Auto-injector

ABSTRACT

Provided is an auto-injector for a syringe suitable for the injected delivery of drug to a patient. The auto-injector comprises a cassette unit arranged for receipt of a syringe. The cassette unit and/or syringe is movable from a rest position, in which the syringe needle tip is within the drive unit housing to a use position, in which the needle tip protrudes from a needle delivery aperture thereof. The auto-injector comprises a drive unit arranged for docking receipt of the cassette unit at a docking position and a drive arrangement. The drive unit is arranged for initial receipt of the cassette unit at an intermediate pre-docking position and for subsequent transport of the cassette unit to the docking position. In embodiments, the drive unit is arranged such that transport of the cassette unit to the docking position is permitted only following verification of an identifier at the intermediate pre-docking position.

CROSS-REFERENCE TO RELATED APPLICATION

This application claims the benefit of U.S. Provisional PatentApplication No. 61/492,530, filed Jun. 2, 2011, which is herebyincorporated by reference herein in its entirety.

BACKGROUND

The present invention relates to an auto-injector device for receipt ofa syringe that is suitable for use in the injected delivery of a drugformulation to a patient.

It is well-known to use syringes for the delivery of injectable liquiddrug formulation to a patient. Syringes rely on puncturing of thepatient's skin by a hollow needle through which the injectable liquiddrug (e.g. in solution or suspension form) is delivered to the muscle ortissue of the patient. Typically, syringes comprise a barrel forcontaining a volume of the liquid drug; a hollow needle defining aneedle tip for dispensing of the liquid; and a plunger that is axiallymovable within the barrel.

It is also well-known to provide auto-injectors for use with syringes.Such auto-injectors typically comprise a body for housing the syringeand an actuating mechanism, which is triggered in use, to allow forautomatic delivery of the liquid drug formulation from the syringe.Actuating mechanisms typically comprise a source of drive (e.g. a strongspring) for drivable movement of a drive transfer element (e.g. aplunger rod) that transfers drive to the plunger for axial movementthereof within the syringe barrel. Such movement of the plunger resultsin the plunged driving of the liquid drug from the syringe barrel to thehollow needle for dispensing to the patient via the needle tip thereof.

For safety and hygiene reasons, it is desirable that the hollow needledoes not protrude from the housing of the auto-injector other than whenexpelling the liquid drug formulation during an injection procedure.Thus, auto-injectors have been developed in which, the housing isarranged such that a needle receiving part allows for the needle of thesyringe to be axially moveable therein from a first (i.e. rest) positionin which the hollow needle is shrouded by the needle receiving part to asecond (i.e. use) position in which at least the tip of the needleprotrudes from that needle receiving part of the housing for penetratingthe skin of the patient to an injection position. Only when the needleis at such injection position should it be possible for drug delivery tocommence. Thus, auto-injectors have been developed which provide a twostage actuating mechanism, which first acts to transfer drive force tomove the syringe from the ‘rest’ to the ‘use’ position, and which onlythen secondly acts to transfer drive force to the plunger for expellingof liquid drug contents from the syringe barrel.

The majority of auto-injectors are configured as a single device thatincorporates both syringe and actuating mechanism in the same devicehousing. It is common for such devices to be arranged to be disposablesuch that following injected delivery of the liquid drug formulation,and typically also following retraction of the syringe back into thehousing, the whole device may be safely disposed of.

SUMMARY

It has been proposed to configure auto-injectors to include anelectrically powered source of drive. Such configurations areparticularly suitable for use by patients whose manual dexterity is socompromised (e.g. due to severe arthritis) that electrical powering isof real practical assistance. The use of electrically powered drivesystems can also allow for more complex drive arrangements (e.g. twospeed injection procedures) to be engineered. Furthermore, electricalpowered devices can also be arranged to include electrical controlsystems and electronic data management systems including those thatprovide information and feedback to the patient by means of a suitableuser interface.

In some situations, it is undesirable for an electrically poweredauto-injector to be fully disposable. Auto-injectors disclosed herein,in certain embodiments, include both a re-useable drive unit comprisingan electrically powered source of axial drive and a cassette unitcomprising a syringe, which releasably interfits with the drive unit andcan be arranged to be disposable. The housing of the drive unit definesa docking cavity arranged for docking receipt of the cassette unit at adocking position. Such auto-injectors may be ‘environmentally friendly,’where the majority of components are retained to be used for furtherinjection procedures. It also allows for the drive unit to be fittedwith additional features such as electronics, which may not be costeffective on a completely disposable device.

The cassette unit comprises a cassette unit housing defining a cassetteunit housing cavity. The cassette unit housing cavity is arranged forreceipt of a standard syringe comprising a barrel for containing avolume of a liquid drug formulation, a hollow needle at a front end ofsaid barrel defining a needle tip for dispensing of the liquid drugformulation and a plunger that is axially movable within the barrel.Either the syringe or the cassette unit and syringe held thereby ismovable within the drive unit housing from a rest position, in which theneedle tip of the syringe is within the drive unit housing to a useposition, in which the needle tip protrudes from a needle deliveryaperture of the drive unit housing.

The drive unit includes a drive arrangement comprising an electricallypowered source of axial drive. In certain implementations, the driveunit includes a first drive transfer element for transferring the axialdrive to the cassette unit for advancing the syringe to said useposition, and a second drive transfer element for subsequentlytransferring the axial drive to the plunger of the syringe for movingthe plunger into the barrel of the syringe to eject at least part of thevolume of liquid drug formulation.

One problem associated with the use of such an auto-injector having are-useable drive unit and a separate cassette unit is to ensure that thecassette unit is correctly received at the docking position within thedrive unit housing.

In solution, the drive unit of the auto-injector herein is arranged forinitial receipt of the cassette unit at an intermediate pre-dockingposition and for subsequent transport of the cassette unit to thedocking position. That transport of the cassette unit to the dockingposition is in embodiments, by automatic control under the action of theelectrically powered source of drive.

Another problem associated with the use of such an auto-injector havinga re-useable drive unit and a separate cassette unit is to ensure thatonly the correct cassette unit containing the appropriate drug anddosage for the patient is loaded into the drive unit in readiness forinjected drug delivery to the patient. Sub-problems include ensuringthat only a fresh (i.e. not past expiry date) and/or unused cassette isso loaded. Some method of verifying and checking the contents of thecassette unit is thus, desirable. At a very basic level, the cassetteunit can incorporate drug/dosage labelling, and perhaps including ‘voidif torn’ type stickers to show if the cassette has been tampered with orused previously. However, it would be advantageous to provide a moresophisticated way of enabling this process, which does not rely onpatient checking, which may break down for example if the patient haspoor eyesight and/or suffers from an ailment, which impairs cognitiveand recognition skills.

In solution to the above-mentioned problems, the drive unit of thepresent auto-injector is arranged to receive the cassette unit housing(e.g. at an intermediate pre-docking position) to allow for verificationthereof. Such verification can include for example, checking of drug anddosage information such as against patient prescription details,checking that the drug is not past its expiry date and/or subject to alot recall and/or checking that the cassette has not been usedpreviously. In embodiments, the cassette unit is provided with anidentifier, which comprises such data in a form that may be readilysubject to automated interrogation. In embodiments, the drive unitcomprises a reader for reading (interrogating) said identifier and, incommunication with said reader, a verifier for verifying saididentifier. In embodiments, the drive unit is arranged such thattransport of the cassette unit to the docking position is permitted onlyfollowing positive verification of the identifier at the intermediatepre-docking position. Thus, only appropriately identified cassette unitsare finally receivable into the device for drug delivery there from.

According to one aspect of the present invention there is provided anauto-injector comprising

(a) a cassette unit comprising a cassette unit housing defining acassette unit housing cavity, said cassette unit housing cavity arrangedfor receipt of a syringe comprising

-   -   a barrel for containing a volume of a liquid drug formulation;    -   a hollow needle at a front end of said barrel, said hollow        needle defining a needle tip for dispensing of said liquid drug        formulation; and    -   a plunger that is axially movable within the barrel; and        (b) a drive unit.

In certain implementations, the drive unit includes a housing defining adocking cavity and a needle delivery aperture, wherein said dockingcavity is arranged for docking receipt of said cassette unit at adocking position. The cassette unit and/or said syringe is movable froma rest position, in which the needle tip of the syringe is within thedrive unit housing to a use position, in which the needle tip protrudesfrom said needle delivery aperture.

The auto-injector may also include a drive arrangement comprising

-   -   one or more electrically powered sources of axial drive;    -   a first drive transfer element for transferring said axial drive        to the cassette unit and/or to the syringe for advancing the        syringe to said use position; and    -   a second drive transfer element for subsequently transferring        the axial drive to said plunger of the syringe for moving the        plunger into the barrel of the syringe to eject at least part of        said volume of liquid drug formulation,        wherein said drive unit is arranged for initial receipt of the        cassette unit at an intermediate pre-docking position and for        subsequent transport of the cassette unit to the docking        position.

In embodiments, the drive unit is arranged for automated verification ofthe cassette unit (e.g. at the intermediate pre-docking position or atthe docking position), and the cassette unit further comprises anidentifier and the drive unit further comprises a reader for readingsaid identifier and, in communication with said reader, a verifier forverifying said identifier.

In embodiments, the drive unit is arranged such that transport of thecassette unit to the docking position is permitted only followingpositive verification of the identifier at the intermediate pre-dockingposition.

These and other embodiments are set forth in the later description,which describes for illustrative purposes only various embodimentsthereof.

In relation to aspects of the auto-injector device described herein theterm ‘forward’ is used to mean that end of the device, which locatesclosest to the injection site in use (i.e. the needle tip end) and theterm ‘rear’ or ‘rearward’ is used to mean that end of the device, whichlocates furthest from the injection site in use.

There is provided an auto-injector device that is arranged for use witha syringe that contains a liquid drug formulation. The syringe isarranged to be suitable for use in the injected delivery of the liquiddrug formulation to a patient.

The auto-injector comprises both a drive unit and a cassette unitreceivable by the drive unit. The individual drive unit and cassetteunit parts thereof comprise further separate aspects of the presentinvention. In embodiments the drive unit and cassette unit are providedas a kit of parts.

Cassette Unit

The cassette unit comprises a cassette unit housing defining a cassetteunit housing cavity. The cassette unit housing cavity is arranged forreceipt of a syringe and is therefore typically sized and shaped forthis purpose. The cassette unit housing may be arranged as a single partor a multi-part (e.g. two part) cassette unit housing assembly.

In embodiments, the syringe is held in generally fixed fashion withinthe cassette unit housing. In other embodiments, the syringe is movablewithin the cassette unit housing such as in a direction parallel with oralong the drive axis.

In embodiments, wherein the syringe is held in generally fixed fashionwithin the cassette unit housing, at least the needle tip of the syringenormally protrudes out of the cassette unit housing cavity such as froma needle projection aperture thereof.

In other embodiments, the syringe is movable within the cassette unithousing from a first position, in which the needle tip of the syringe iswithin the cassette unit housing to a second position, in which at leastthe needle tip protrudes from a needle projection aperture thereof.

The syringe that is receivable within the cassette unit housing cavitycomprises a syringe barrel for holding a volume of the liquid drugformulation; a hollow needle at a front end of the barrel, the hollowneedle defining a needle tip for dispensing of said liquid drugformulation; and a plunger (e.g. in the form of a rubber stopper) thatis axially movable within the syringe barrel. The syringe plunger ismovable axially within the barrel so as to enable the liquid drugformulation to be expelled from the barrel and thence through the hollowneedle via the dispensing tip for injection into the patient. Thesyringe barrel is typically, comprised of glass but may also becomprised of a relatively hard plastic polymer such as hardenedpolyethylene, polycarbonate or cyclic olefin polymers.

In embodiments, the plunger is comprised of a natural or syntheticpolymer friction material, which frictionally interacts with the sidewall of the syringe barrel. Suitable plunger materials include naturalor synthetic rubbers or elastomeric materials.

In more detail, the syringe barrel is selected such as to define abarrel chamber for containing a suitable volume of the liquid drugformulation. In embodiments, that suitable volume is selected tocorrespond to a single dose of the drug formulation to be delivered tothe patient. In other words, delivery of that single dose involvesexpelling all of the liquid drug formulation contents of the barrelchamber through the hollow needle for injection into the patient.

In embodiments, the rear end of the syringe barrel is provided with anend flange. In embodiments, the forward end of the syringe barrel isshaped to provide a shoulder. In embodiments, forward of that shoulderthe syringe narrows further into a neck, which typically forms theneedle-holding part thereof.

In embodiments, the needle barrel is provided with a barrel sleeve thatis arranged to fit over part or all of the length of the needle barrel.The barrel sleeve may also extend out beyond the syringe barrel towholly or partly enclose a length of the forward shoulder of the syringebarrel and of the hollow needle that extends from (the forward shoulder)of the syringe barrel.

In embodiments, the cassette unit is arranged to accommodate multiplesyringe sizes. Common sizes of syringe include the 2.25 ml syringe andthe 1 ml ‘long’ syringe, which has a smaller syringe barrel diameter.

In embodiments, accommodation of multiple syringe sizes within the samecassette unit geometry is achievable by providing suitable adapters tothe barrel of the syringe. In embodiments, sleeve form adapters areemployed.

In embodiments, the sleeve form adapter is arranged for receipt by thesyringe barrel and fits at least partly over the flange of the rear endof the syringe barrel. In embodiments, the sleeve adapter is arrangedfor snap fitting over the end flange of the syringe. In embodiments, theflange is effectively capped by the relevant ‘end flange’ part of thesleeve form adapter.

In embodiments, a major portion of the syringe barrel and end flangethereof is in use, sleeved by the sleeve form adapter. The overalleffect of this sleeving of a major portion is firstly to increase theeffective diameter of the syringe barrel; secondly to providestrengthening reinforcement to the end flange; and thirdly to increasethe effective length of the syringe.

In one particular embodiment, the cassette unit is shaped and sizedbased on the geometry of the larger 2.25 ml syringe. A syringe having asmaller outer dimension (e.g. a 1 ml ‘long’ syringe) may then beaccommodated in this same cassette unit by use of a sleeve adapter thateffectively functions to adapt the outer syringe geometry (e.g. theouter diameter thereof) to closely correspond to or to be identical withthat of the 2.25 ml syringe.

In embodiments, adding a sleeve adapter to the smaller diameter 1 ml‘long’ syringe can make it slightly longer than the 2.25 ml syringe. Inembodiments, when the cassette unit is assembled with the 2.25 mlsyringe, an adapter ring may be added underneath the syringe flange tomake its effective flange thickness the same as that of a smaller 1 mlsyringe with a sleeve adapter.

In embodiments, the sleeve adapter is provided with one or more slits inthe wall(s) of the sleeve adapter such as to define flexible fingers,which allow the adapter to flex open. In embodiments, the presence ofsuch flexible fingers is of utility during assembly of the sleevedsyringe as the needle cover (e.g. rigid needle shield), which typicallyhas a larger diameter than the syringe barrel, passes through the centreof it when the syringe is pressed into the adapter. In embodiments, theend flange at the rear end of the syringe then snaps into the rear endof the adapter such that the syringe is locked into the adapter onceassembled.

In embodiments, one or more positioning and/or retaining features areprovided to the cassette unit housing for positioning and/or retainingthe syringe and sleeve form adapter in the cassette unit housing cavity.In embodiments, the one or more positioning and/or retaining featurescomprise one or more snap features provided interiorly to the cassetteunit housing.

In certain implementations, the ability of the cassette unit toaccommodate syringes of different sizes confers certain advantages. Inthe case of drive units with a variable performance across the injectionstroke it may be advantageous in some circumstances to use a syringe oflarger bore diameter because the same volume of drug can be deliveredfrom a shorter injection stroke, thereby enabling the drive unitperformance to be optimized.

Similarly, for a given combination of needle and drug (same needle boreand viscosity) the volume injected per unit displacement of the plungeris greater in the case of a wider bore syringe by a factor proportionalto the square of the difference in syringe diameter. A faster injectioncan therefore be achieved for the same plunger displacement velocity. Inthis case the force applied by the plunger will be greater in the largersyringe due to the increase in volumetric flow rate. This may be usefulin cases where the maximum displacement velocity is limiting.

Also, the flexibility in dose delivery rate provided by variable syringesizes may also be beneficial in optimizing the power requirements of theelectrically powered drive unit. Thus, in embodiments this may limitpeak current drain of the batteries thereby enabling smaller batteriesto be used, maximizing the time between recharge or replacement and/orprolonging their useful life.

It has been appreciated that to reduce the risk of the syringeshattering under the loads associated with injecting the drug, it isimportant for a majority of the load path to travel through the shoulderat the forward end of the syringe and lesser load to pass through theflange at the rear end of the syringe.

In embodiments, the forward shoulder of the syringe is provided with oneor more shoulder support features. In embodiments, the one or moreshoulder support features are integral (e.g. integrally formed) with thecassette unit housing. In other embodiments, the one or more shouldersupport features are defined by one or more separate shoulder supportparts provided to the cassette unit.

In embodiments, the one or more shoulder support features locate (e.g.in snap-fit arrangement) between the needle cover (e.g. rigid needleshield) and the forward shoulder of the syringe. In embodiments, thesleeve adapter as described above, is provided with such one or moreshoulder support features that in embodiments, snap-fit between theneedle cover (e.g. rigid needle shield) and the forward shoulder of thesyringe. This snap fitting is typically enabled after the syringeassembly has been pressed through the sleeve adapter during the assemblyoperation.

In embodiments, a clearance space is defined between the bottom of thesyringe flange and the closest surface of the sleeve adapter. Inembodiments, the sleeve form adapter acts to space the end flange of thesyringe from the inner walls of the cassette unit housing. Inembodiments, when the syringe is loaded within the cassette unit housingthe flange of the syringe is spaced from the inner walls of the cassetteunit housing and/or the sleeve adapter and in embodiments, is not incontact with anything.

In embodiments, a ring of compliant (e.g. resilient or flexible)material such as rubber or a suitable synthetic polymeric material isemployed to bear some of the load on the flange and/or to accommodatetolerances. In embodiments, that ring of compliant material is arrangedfor receipt over the shoulder support feature. In embodiments, the ringof compliant material acts such as to secure the shoulder supportfeature in place such as by securing a snap-fit arrangement in place.

In embodiments, at least part of the syringe or syringe/sleeve adaptercombination interacts with (e.g. inserts into) a constraining feature ofthe cassette unit housing that has a tight clearance between its innerwalls and the outside diameter of the standard (e.g. 2.25 ml) syringe.In embodiments, this constraining feature of the cassette unit housinginteracts with the shoulder and/or neck of the syringe. In embodiments,this feature is the only surface acting to constrain the position of thesyringe within the cassette unit housing (e.g. during injection). Inembodiments, the constraining feature of the cassette unit housing thatconstrains the syringe also prevents the sleeve adapter from flexingoutwards when the injection loads are applied to the syringe. With therear end of the sleeve adapter (e.g. any defined fingers thereof)securely snapped under the shoulder of the syringe and so prevented fromflexing outwards, the syringe is effectively secured within the cassetteunit housing. In embodiments, if this were not the case the forceapplied to the syringe during injection could push the fingers open andenable the syringe to push through.

The hollow needle defines a needle bore, which is most typically ofcircular cross-section and of selected bore diameter. It may beappreciated that in embodiments, the bore diameter may affect the forcerequired to expel the liquid drug formulation through the needle andalso the velocity at which the liquid drug formulation is expelled.

The selected needle bore may also, in embodiments affect the degree ofpatient discomfort during injection. Smaller bore diameters, typicallyprovide more patient comfort, whereas larger bore diameters enable morerapid/lower force delivery of the liquid through the needle. Acompromise is therefore needed in selecting a needle bore to provideacceptable patient comfort and liquid delivery through the needlecharacteristics.

Examples of typical needles that are suitable for use therein include12.5 mm (“half inch”) long thin wall needles of grade 23G, 25G or 27G.These have a needle bore of from about 0.2 to 0.4 mm such as from 0.25to 0.35 mm. Other examples include both regular and thin wall needlesused in conventional syringes including those with bevels such as 3 and5 bevels.

The cassette unit housing and any inner cassette unit housing subassembly thereof is shaped to define a cassette unit housing cavitywithin which the syringe is receivable, and in embodiments, a needleprojection aperture. The cassette unit housing cavity is typicallycylindrical in form, thereby matching the typically cylindrical outerprofile of a syringe. The cassette unit housing cavity may be furthershaped with any manner of grooves, indentations or other shaping orsurface details to define a ‘lock and key’ relationship between thecassette unit housing and any inner cassette unit housing sub assemblythereof and the syringe. Colour guides, arrows and any other surfacemarkings may also be employed.

Typically, the cassette unit housing and/or any inner cassette unithousing sub assembly thereof is provided with a barrel receiving partfor receiving the barrel of the syringe; a plunger receiving part forreceiving the plunger of the syringe; and in embodiments, a needlereceiving part for receiving the hollow needle of the syringe.

In embodiments, the plunger receiving part of the cassette unit housingand/or any inner cassette unit housing sub assembly thereof allows theplunger within the syringe barrel to be received thereby and for theplunger to be movable (e.g. axially) therein from a first position to asecond position, in which it is moved somewhat into the syringe barrel.During use the plunger is in embodiments, movable to a fully plungedposition in which most, in embodiments all of the liquid drugformulation contents of the barrel have been expelled.

In embodiments, the needle receiving part of the cassette unit housingand/or any inner cassette unit housing sub assembly thereof includes aneedle projection aperture through which the hollow needle may protrudefrom the housing, for example during expelling of the liquid drugformulation through the hollow needle and its needle tip for delivery tothe patient.

In embodiments, the syringe is movable within the cassette unit housingcavity from a rest position, in which the needle tip is within thecassette unit housing to a use position, in which the needle tipprotrudes from the needle projection aperture. In other embodiments, thesyringe is in fixed relationship with the cassette housing in which,typically the needle tip protrudes from the needle projection aperture.

Where the syringe is movable in the cassette unit housing, it maydesirable for safety and hygiene reasons that the needle does notprotrude from (i.e. out with) the cassette unit housing other than whenexpelling the liquid drug formulation during an injection procedure.Thus, the cassette unit housing and/or any inner cassette unit housingsub assembly thereof and cassette unit housing cavity defined thereby isgenerally arranged such that the needle receiving part thereof allowsfor the needle of the syringe to be axially moveable therein from afirst position in which the needle is wholly housed (or shrouded) by theneedle receiving part to a second position in which at least the tip ofthe needle protrudes from that needle receiving part of the cassetteunit housing.

In embodiments, where the syringe is movable within the cassette unitthe cassette unit housing includes biasing means (e.g. a spring)arranged such that the needle is normally biased towards the firstposition, wherein such biasing means are overcome during the actuationof the syringe (e.g. by an actuating mechanism) to allow for movement ofthe needle to the second position.

In embodiments, it is desirable for cassette unit housing to allow forthe needle of the syringe to be retracted into the housing after use.Thus, it is desirable to be able to retract the needle back into theneedle receiving part of the cassette unit housing after the injectionprocedure, that is to say to retract the needle from the second positionto a retracted position that may in embodiments, correspond to the firstposition or in other embodiments, correspond to a third position, whichin embodiments is further away from the needle projection aperture. Aneedle retract mechanism may thus, be provided to the cassette unithousing (e.g. responsive to a biasing means such as a light returnspring) to retract the syringe needle back into the cassette unithousing.

In embodiments, it is desirable for the cassette unit housing to allowfor the needle of the syringe to be shrouded by a needle shroud elementafter use. Thus, in particular it is desirable to be able to provide ameans of shrouding the needle of the syringe that is moved or otherwisebrought into operation after completion of the injection procedure. Suchmeans in embodiments comprises a movable shroud element that is adaptedto be movable to a shrouding configuration at the end of the injectionprocedure.

In embodiments, the cassette unit housing is provided with a removablecap that fits over and thereby, acts such as to close off, the needleprojection aperture. It may therefore, be appreciated that when in thecapped position, the removable cap acts such as to prevent ingress ofcontaminants into the needle receiving part of the housing.

In embodiments, the syringe further comprises a needle cover defining aneedle sheath arranged in a sheathing configuration for sheathing (e.g.sealing) of the needle tip.

In embodiments, the needle sheath is comprised of a (e.g. resiliently)compressible material such as a natural or synthetic rubber material. Ina storage configuration, the needle tip sticks into (e.g. is spiked orstaked into) the needle sheath such that sealing of the needle tip isachieved. Usually, at least the first 3 to 4 mm of the needle tip end isso sheathed. It will be appreciated that for clinical reasons, thesealing of the needle tip acts in embodiments, such as to preventpassage of contaminant, bacterial or otherwise, through the needle tipand thus into the needle bore and syringe barrel chamber. Sterilesealing is preferred.

In embodiments, the needle cover is provided with a needle sheath coverfor covering the needle sheath thereof. In embodiments, the needlesheath cover is comprised of a rigid material (e.g. polypropylene). Inembodiments, the needle sheath cover is provided with one or moregripping elements (e.g. hooks) arranged for gripping of the needlesheath. In embodiments, the needle sheath is provided with one or morefeatures arranged for receipt of the one or more gripping elements suchas one or more indents, grooves or cavities.

In embodiments, the needle cover is provided to (e.g. fixed to orintegral with) a removable cap for the cassette unit housing. Thus, inembodiments, the needle cover projects within the cap such that when theremovable cap is in the capped position the needle sheath and any needlesheath cover therefor projects towards the needle tip of the syringe. Insuch embodiments, when in the capped position, the needle tip issheathed by the needle sheath, and when the cap is removed the needlesheath and any needle sheath cover therefor are also removed such as tothereby, unsheathe the needle tip. In embodiments, the removable capdefines an essentially closed cylindrical cap chamber, optionallytapering, and the needle sheath and any needle sheath cover are providedalong the axis of that cylindrical chamber.

In embodiments, the interior of the removable cap is provided with aconnector defining one or more needle cover gripping elements forgripping the needle cover (i.e. gripping the needle sheath and/or anyneedle sheath cover therefor). In embodiments, such gripping elementsare arranged for gripping of the needle cover when in the cappingposition. In embodiments such gripping elements are (e.g. additionally)arranged for gripping of the needle cover on removal of the cap suchthat removal of the cap also results in removal of the needle cover andhence, unsheathing of the needle tip. In embodiments, the needle covergripping elements are arranged to project away from the top innersurface (e.g. of the cylindrical cap chamber) of the removable cap andtowards its open end.

In embodiments, the connector comprises one or more needle covergripping elements (e.g. gripping legs) attaching to a central hub. Inembodiments, the connector is in the form of a cage-like needle covergripper. In embodiments, each gripping element (e.g. leg) is provided(e.g. at the foot thereof) with one or more gripping protrusions such asone or more internally facing hooks or barbs. In embodiments, theinternally facing hooks or barbs are disposed at an angle with respectto the gripping leg. In embodiments, the connector locates within theremovable cap such that the central hub locates adjacent to or slightlyspaced from the top inner cap wall or surface and the gripping legsproject away from the top inner cap wall or surface and towards the openend of the cap. Other needle cover gripper arrangements are disclosed inApplicant's co-pending PCT publication no. WO2009/081103 the entirecontents of which are incorporated herein by reference.

In embodiments, the removable cap is provided with a connector. Theconnector is shaped to fit within and engage the needle cover and toengage the inner part of the removable cap. In embodiments, theconnector includes one or more needle gripper elements in the form offirst legs attaching to a central hub and spaced symmetrically away fromone another, each first leg having one or more internally facing barbspointing toward a forward region of the connector and adapted to engagea proximal region of the needle cover. In embodiments, the one or moreinternally facing barbs are disposed at an angle with respect to thefirst leg. In embodiments, the connector also includes one or moresecond legs spaced symmetrically away from one another, each second leghaving one or more externally facing barbs located in the forward regionof the connector and adapted to engage a forward region of the innerpart of the removable cap. In embodiments, the one or more first legsare biased initially at about 60 to 80 degrees with respect to thehorizontal. Arrangements of removable cap and connector of this type aredisclosed in Applicant's co-pending PCT publication no. WO2009/090499the entire contents of which are incorporated herein by reference.

In embodiments, the geometry of the removable cap is selected to allowfor the needle cover to be sufficiently aligned with the needle of thesyringe so that on re-capping the needle does not undesirably catch onthe needle sheath inside the needle cover. In embodiments, wherein theconnector comprises one or more needle cover gripping elements (e.g.gripping legs) attaching to a central hub, Applicant has found that toassist re-sheathing of the needle cover it is desirable to position theconnector within the removable cap such that the central hub is inspaced relationship to the top inner cap wall of the removable cap. Whenso-positioned, the gripping legs project away from the top inner capwall and towards the open end of the cap.

Applicant has found that having the central hub in somewhat spacedrelationship to the top inner cap wall allows for a certain ‘give’ inthe axial position of the needle cover such that in the event of anysnagging of needle cover by the needle tip during re-sheathing, theconnector and/or needle cover is free to move into the ‘give’ space,thereby ensuring that the snagging event does not result in any bending,or in a worst case scenario snapping, of the needle. The occurrence ofany needle stick hazards during re-capping and re-sheathing is thus,minimized. In addition, the presence of ‘give’ space ensures that it isalways possible to refit the cap, which may otherwise be prevented byneedle snagging.

In embodiments, the removable cap is provided with a spacer insert andthe connector is provided to (e.g. locates within) the spacer insert. Inthese embodiments, the function of the spacer insert is effectively toassist in defining of the ‘give’ space as described above. Inembodiments, the spacer insert defines a central end hub and an innerboss, which extends from the central end hub to define a chamber forreceiving the connector and in embodiments also, in use for receivingthe needle cover as gripped by the connector. In embodiments, the spacerinsert also defines an outer boss, which extends from the end hub and inembodiments, also extends about (e.g. circumferentially about) the innerboss. In embodiments, the outer boss includes crenellated portionstherein. In embodiments, the outer boss defines flexible fingers, whichsplay out from the central end hub and thus, extend about the outersurface (e.g. of the lower part of) the outer boss. In embodiments, theflexible fingers of the outer boss locate within the crenellatedportions of the outer boss. In embodiments, the spacer insert iscomprised of a plastic (e.g. a plastic polymer) material and thus, maybe referred to as a plastic ‘outer flower’ structure. In embodiments,the chamber of inner boss of the spacer insert is provided with aconnector (e.g. a needle cover gripper such as in the form of acage-like structure) and defining plural gripping elements arrangedabout a central hub. In embodiments, the connector is comprised of ametal and may thus, be referred to as a metal ‘inner flower’ structure.

To assist with re-sheathing of the needle cover on re-capping of thecassette unit after an injection procedure, the position of spacerinsert and connector held there-within is in embodiments, arrangedwithin the removable cap such that central end hub of the spacer insertis in spaced relationship to the effective end wall of the removablecap. By effective end wall it is meant either the actual end wall of theremovable cap or a structure (e.g. ledge-like structure) that functionsas a seat for the central end hub of the spacer insert and thus, definesthe minimum spaced relationship between that central end hub and the endof the removable cap. Having the central end hub of the spacer insert insomewhat spaced relationship to the effective end wall of the removablecap allows for a certain ‘give’ in the axial position of the connectorand needle cover gripped thereby such that in the event of any snaggingof needle cover by the needle tip during re-sheathing, the spacerinsert, connector and needle cover are free to move into the ‘give’space, thereby ensuring that the snagging event does not result in anybending, or in a worst case scenario snapping, of the needle. Theoccurrence of any needle stick hazards during re-capping andre-sheathing is thus, minimized.

In embodiments, the removable cap is provided with a finger-grip featurethat is sized and shaped for gripping by the finger of a user and toprovide a ready means for removing the cap and needle cover attachedthereto. In embodiments, the finger-grip feature is shaped to provide aring (e.g. a gripping ring or ring pull) for ready finger gripping bythe user by placing a finger or thumb inside the ring.

In embodiments, the removable cap is provided with one or more firstengagement features arranged for selectively engaging one or more secondengagement features of the cassette unit housing when the cap is in thecapping position. Thus, in the capping position an engaging relationshipmay (e.g. selectively) be established between the removable cap and thecassette unit housing.

In embodiments, the first engagement features of the removable cap andthe second engagement features of the cassette unit housing are arrangedto have any form, which allows for engaging relationship to beestablished. In embodiments, latching, peg and socket and snap-fitfeatures arranged for mutual engagement are envisaged.

In embodiments, the removable cap is provided (e.g. at the brim thereof)with an arrangement of first engagement features that are sized andshaped to extend up into the cassette unit housing when the cap is inthe capping position. In embodiments, the arrangement of firstengagement features is in the form of a crown of such first engagementfeatures. In embodiments, that crown is defined by an arrangement ofprotruding arms having shaped tips.

In embodiments, the cassette unit housing is provided (e.g. at theforward end thereof) with an arrangement of second engagement featuresthat are sized and shaped to extend up into the removable cap when thecap is in the capping position. In embodiments, the arrangement ofsecond engagement features is in the form of a crown of such secondengagement features. In embodiments, that crown is defined by anarrangement of protruding arms having shaped tips.

In embodiments, the first engagement features of the removable cap arearranged for engaging with features of the inner cassette unit housingand optionally, also with features of the syringe. In embodiments, thatengaging is by latch engagement or snap engagement of the engagementfeatures of the cap with features of the inner cassette unit housingand/or features of the syringe.

In embodiments, the second engagement features of the cassette unithousing are arranged for engaging with (e.g. inner) features of theremovable cap. In embodiments, that engaging is by latch engagement orsnap engagement of the engagement features of the cassette unit housingwith features of the (e.g. inner part of the) removable cap.

In embodiments, the one or more first engagement features of theremovable cap are arranged for selective engagement with the one or moresecond engagement features of the cassette unit housing (e.g. of theinner wall(s) thereof) such that when so-engaged rotation of the cap andhence of any needle cover attaching thereto (e.g. by means of aconnector) is restricted or prevented. Such restriction/prevention ofcap rotation has been found to be desirable to prevent any damage to thesyringe needle within the needle cover as may potentially result fromany unintended/undesirable rotation (e.g. non-symmetric or off centralaxis rotation) of the cap and hence connector and needle cover relativeto the needle.

In embodiments, the cassette unit housing and removable cap are arrangedsuch that when the removable cap and needle cover connecting thereto arebrought into capping relationship (i.e. moved towards the cappingposition) the one or more first engagement features of the removable capmove into engaging relationship with the one or more second engagementfeatures of the cassette unit housing. The establishment of thisengaging relationship acts such as to prevent rotation of the cap, andhence also of the needle cover attaching thereto.

In particular embodiments, during such insertion of the removable capinto the cassette unit housing the tips of the crown of first engagementfeatures of the removable cap snap into second engagement featuresprovided to the walls of the inner cassette unit housing. The protrudingarms of each crown of first engagement features are arranged to fitabout rigid second engagement features of the cassette unit housing suchas to prevent rotation of the cap, and hence also of the needle coverattaching thereto.

In embodiments, the geometry of the removable cap is selected to allowfor the needle cover to be sufficiently aligned with the needle of thesyringe so that on re-capping the needle does not undesirably catch onthe needle sheath inside the needle cover. In embodiments, the geometryof the first engagement features of the removable cap and/or secondengagement features of the cassette unit housing is selected to allowfor such ease of re-capping. In embodiments, the arms of the crown offirst and/or second engagement features are arranged for guiding intothe cassette unit housing e.g. by a guide feature (e.g. lead-in)provided to the inner cassette unit housing. In embodiments, once thefirst engagement features of the removable cap begin to engage with thesecond engagement features of the cassette unit housing it is heldconcentrically enough to prevent the needle from catching on the needlesheath. This is important to ensure that on re-capping the needle coveris able to fully sheathe the used needle to minimize the occurrence ofany needle stick hazards.

In embodiments, the cassette unit is provided with a cap lock (i.e. capremoval prevention) feature for selectively preventing removal of theremovable cap. In embodiments, the cap lock feature is movable from afirst cap locking position in which it prevents removal of the cap fromthe cassette unit to a second cap un-locking position in which it nolonger prevents such cap removal.

In embodiments, the cap lock feature is configured as a shuttle lock,which may shuttle from the first cap locking position to the secondnon-locking position. In embodiments, the cap lock feature is biased tothe first locking position.

In embodiments, the cap lock (i.e. cap removal prevention) featureselectively prevents removal of the removable cap until either thecassette unit locates at the docking position within the drive unithousing or until a release mechanism is activated. In embodiments, thecap lock feature of the cassette unit is only movable from the first caplocking position to the second cap non-locking position when thecassette unit locates at the docking position within the drive unithousing. In embodiments, the cap lock feature is in the first positionduring insertion of the cassette unit into the drive unit and moves tothe second position when the cassette unit is in the docking position inthe drive unit.

In embodiments, the drive unit includes a cap lock release featurearranged such that on moving of the cassette unit towards the dockingposition in the drive unit said cap lock release feature interacts withthe cap lock feature of the cassette unit to move the cap lock featureto the second cap unlocking position when the cassette unit is at thedocking position in the drive unit.

In embodiments, the cap lock feature (e.g. configured as a shuttle lock)includes one or more locking features, which in the cap locking positionact such as to prevent movement (e.g. inwards movement) of one or moreof the first engagement features of the removable cap and/or the secondengagement features of the cassette unit housing.

In embodiments, in the first cap locking position the one or morelocking features locate inwards or outwards of one or more of the firstengagement features of the removable cap and/or of the second engagementfeatures of the cassette unit housing such as to block disengagingmovement (e.g. flexing movement) thereof. Thus, in embodiments, theremovable cap and needle cover attached thereto are locked into thecassette unit when the cap lock (e.g. shuttle lock) is in such a caplocking position because the one or more first engagement features ofthe cap and/or the one or more second engagement features of thecassette unit housing are blocked from disengaging (e.g. by flexingmovement) from their mutually engaging relationship.

In embodiments, the cap lock (e.g. shuttle lock) biases and is biased toa cap locking position. In embodiments, the cap lock (e.g. shuttle lock)is spring loaded so that the cap locking feature biases towards itsfirst cap locking position. In embodiments, when the cap lock (e.g.shuttle lock) is moved forwards in the cassette unit housing, the firstengagement features of the cap and/or second engagement features of thecassette unit housing are free to disengage (e.g. by suitable flexingmovement) from their mutually engaging relationship. Once the cap lock(e.g. shuttle lock) is in this disengaged position, the removable capand hence also the needle cover can be removed from the cassette unit.

In embodiments, the cap lock feature is arranged such that forreplacement of the removable cap onto the cassette unit (e.g. afterinjection use of the syringe) the cap lock feature must be in thesecond, non-locking position.

Thus, in embodiments, the cap lock feature is arranged such that toreplace the needle cover attached to the removable cap back onto thesyringe, the cap lock feature must be in the second, non-lockingposition.

In embodiments, such as where the syringe is movable within the cassetteunit, the cassette unit housing is provided with one or more (e.g.resiliently) flexible elements that extend (e.g. protrude) into thecassette unit housing cavity. In embodiments, the one or more (e.g.resiliently) flexible elements are provided as one or more separateparts that attach or fix to an inner wall of the housing or areotherwise in embodiments, held within the housing. In other embodiments,the one or more (e.g. resiliently) flexible elements are providedintegrally with the housing (e.g. formed as an integral mouldingtherewith). The one or more flexible elements are typically provided tothe needle receiving part of the cassette unit housing. The one or more(e.g. resiliently) flexible elements are desirably arranged to performtwo separate functions.

Generally, in the rest configuration the needle sheath locates to sealoff the needle tip, the one or more (e.g. resiliently) flexible elementscontact the needle cover to restrict (e.g. prevent) movement thereof.Thus, movement of the needle cover is restricted by the action of the(e.g. resiliently) flexible elements, which in embodiments engage withthe needle cover to hold it, and thereby restrict movement thereof. Suchrestriction of movement assists in maintaining the integrity of the sealrelationship between the needle tip and the needle sheath.

In the use configuration, the needle cover is generally removed from theneedle tip such as to unseal that tip. In this use configuration, theone or more (e.g. resiliently) flexible elements flex into the cassetteunit housing cavity to provide a barrier surface. This barrier surfaceacts such as to obstruct the exit of the syringe barrel from thecassette unit housing cavity. Such obstructing function is particularlyimportant in the instance of fracture (i.e. breakage) of the syringe,which is generally comprised of glass material. In this instance, thebarrier surface acts such as to obstruct the exit of fractured parts(e.g. glass shards) of the syringe from the housing cavity. The patientis thereby, protected from coming into contact with such fracturedparts, and thus potential injury in the event of such a syringe fractureevent occurring.

In embodiments, the one or more (e.g. resiliently) flexible elementscomprise a ring comprised of a (e.g. resiliently) flexible material suchas a plastic polymer (e.g. an elastomer) or natural or synthetic rubbermaterial. That ring (e.g. an O-ring) is generally provided to an innerwall of the (cylindrical) cassette unit housing such that the outer ringcircumference thereof attaches to the inner wall of the cassette unithousing. In the rest configuration, the inner ring circumference thereofcontacts the needle cover (e.g. the needle sheath or a needle sheathcover provided thereto) and is somewhat compressed inwards as a resultof that contact, the effect of which is to restrict movement of theneedle cover. In the use configuration, the needle cover is removed, andin the absence of compressive contact with the needle cover, the ringexpands outwards into the cassette unit housing cavity to provide abarrier surface, which acts such as to obstruct the exit of the syringebarrel from the cassette unit housing cavity. In embodiments, thediameter of the uncompressed inner ring circumference of the ring isless than that of the syringe barrel such that when the ring is in itsuncompressed state the syringe barrel may not pass through the ring.

In embodiments, each of the one or more (e.g. resiliently) flexibleelements comprises a flexible finger element comprised of a (e.g.resiliently) flexible material such as a plastic polymer. Each fingerelement is generally provided to an inner wall of the (cylindrical)cassette unit housing such that the finger base thereof attaches to theinner wall of the cassette unit housing. Typically, an arrangement (e.g.circular arrangement) of flexible finger elements is employed such asfrom three to eight finger elements. In the rest configuration, thefinger tip of each finger element contacts the needle cover (e.g. theneedle sheath or a needle sheath cover provided thereto) and is somewhatflexed inwards as a result of that contact, the effect of which is torestrict movement of the needle cover. In the use configuration, theneedle cover is removed, and in the absence of the compressive contactwith the needle cover, the flexible finger element(s) flex into thecassette unit housing cavity to provide a barrier surface, which actssuch as to obstruct the exit of the syringe barrel from the cassetteunit housing cavity. Where the flexible finger elements are provided asa circular arrangement, it is preferable that the diameter of the innercircumferential aperture defined by the extremes of the finger tipsthereof is less than that of the syringe barrel such that when thefinger elements of that circular arrangement flex outwards the syringebarrel may not pass through the inner circumferential aperture definedthereby.

Drive Unit

The auto-injector herein is arranged to allow for actuation (i.e.firing) of the syringe and hence, to allow for injected delivery of drugto a patient. The auto-injector thus, also includes a drive unit fortransferring axial drive to the syringe.

The drive unit comprises a drive unit housing defining a docking cavityand a needle delivery aperture. The docking cavity is arranged fordocking receipt of the cassette unit at a docking position, whereuponsaid cassette unit and/or the syringe is movable from a rest position,in which the needle tip of the syringe is within the drive unit housingto a use position, in which the needle tip protrudes from said needledelivery aperture. The docking cavity and receivable part of thecassette unit are correspondingly sized and shaped to facilitate theintended docking relationship. The drive unit housing may be arranged asa single part or a multi-part (e.g. two part) drive unit housingassembly.

The drive arrangement comprises at least one electrically powered sourceof axial drive. The electrical power may be provided by mains electricalsupply or by a battery, which in embodiments may be rechargeable.

Electrical energy may be conserved by a variety of means to enable theauto-injector to operate for longer on a given source of energy, such asa battery. Energy conservation or saving methods have additionaladvantages in terms of reducing the size requirements of the powersource (e.g. battery) and thus the weight and portability of theauto-injector.

Electrical energy saving methods may be employed to reduce powerconsumption of the drive unit. One such method is to use a clock ortimer circuit to switch the power on and off at regular or predeterminedintervals. In another method a power management system is employed toselectively switch on/off specific electronic functions, such as visualdisplay units or sensors, in order to power these functions only whenthey are required to perform a particular sequence of events. Thusdifferent electronic functions may be switched on and off at varyingintervals and for varying periods under control of a power managementsystem.

In embodiments, the at least one electrically powered source of axialdrive comprises an electrically powered motor. The motor may providelinear or rotary drive, but in general, rotary motors used incombination with suitable gearing arrangements are most suitable. Themotor may for example, comprise a DC electric motor, a piezoelectric(PZ) motor, an ultrasonic motor, a solenoid motor or a linear motor. Inembodiments, the electronic drive system comprises a DC motor, a PZmotor, a stepper motor or an ultrasonic motor. Embodiments are envisagedin which, plural electrically powered sources of axial drive areemployed such as a different drive source (e.g. motor) for each of thefirst and second drive transfer elements.

The drive arrangement comprises a first drive transfer element fortransferring axial drive to the cassette unit and/or the syringe foradvancing the syringe to said use position; and a second drive transferelement for subsequently transferring axial drive to the plunger of thesyringe for moving the plunger into the barrel of the syringe to ejectat least part of the volume of liquid drug formulation.

In embodiments, the first and second drive transfer elements areconfigured as separate parts. In other embodiments, the first and seconddrive transfer elements are in coupling relationship (e.g. via one ormore coupling elements) or form an integral part of a single (i.e.composite) drive transfer element.

In embodiments, the source of axial drive is configured to selectivelyconfer axial drive to the first and second drive transfer elements. Anymanner of gearing and/or coupling arrangements may be employed toachieve this purpose.

In embodiments, the drive arrangement comprises one or more lead screwdrive mechanism. In other embodiments, the drive arrangement comprisesone or more rack and pinion drive mechanisms. In embodiments, any ofsuch drive mechanisms directly comprise the first and/or second drivetransfer elements. In other embodiments, any of such drive mechanismsmay be arranged to communicate with the first and/or second drivetransfer elements by suitable gearing or coupling arrangements.

In embodiments, the electrically powered source of drive is able toexert an axial drive force of up to 60N via the first and/or seconddrive transfer elements to the syringe. In embodiments, the forceexerted may be arranged to vary over the actuation profile such as froma range of 60 to 40N at the start of actuation to from 40 to 20N at theend of the actuation profile.

In embodiments, release of axial drive force (e.g. actuation of theelectrically powered source of drive) is responsive to a trigger (e.g. auser-actuable trigger). In embodiments, the trigger comprises a button,switch or lever arrangement. In other embodiments, a press actuationmechanism that is actuable in response to pressing of the drive unithousing against the skin of a patient is also envisaged. In otherembodiments, a skin sensor mechanism is provided to the drive unithousing that is actuable in response to sensing of the skin of thepatient.

Axial drive force applied to the first drive transfer element results indrivable movement of the syringe from the rest to the use position. Inembodiments, the first drive transfer element communicates directly with(e.g. contacts or abuts) the syringe barrel for transferring drivethereto. In embodiments, the first drive transfer element communicatesdirectly with (e.g. contacts or abuts) the cassette unit fortransferring drive thereto, and thus results in drive being transferredto the syringe barrel. In embodiments, the first drive transfer elementcommunicates indirectly with (e.g. via a slaving or coupling element)the syringe barrel and/or the cassette unit for transferring drivethereto.

In embodiments, the first drive transfer element communicates directlyor indirectly with a cassette unit holder that holds the cassette unitand syringe thereof within the drive unit such as to transfer drive tothe cassette unit holder to thereby result in drivable movement of thesyringe from the rest to the use position.

Axial drive force applied to the second drive transfer element (e.g.plunger rod) results in drivable movement of the plunger within thesyringe barrel, ultimately to a fully plunged position when most, inembodiments all, of the liquid drug formulation contents of the syringebarrel have been drivably expelled therefrom.

In embodiments, the second drive transfer element communicates directlywith (e.g. contacts or abuts) the plunger of the syringe fortransferring drive thereto. In embodiments, an end portion of the seconddrive transfer element directly communicates with (e.g. contacts orabuts) the plunger. In other embodiments, the second drive transferelement communicates indirectly with (e.g. via a slaving or couplingelement) the plunger of the syringe for transferring drive thereto. Incertain other embodiments, an end portion of the second drive transferelement indirectly communicates with the plunger such as via a washer orother intermediate element.

In embodiments, the first and/or second drive transfer element takes theform of a screw drive element or rod drive element, but other suitableforms are also envisaged.

In embodiments, the drive arrangement includes a first coupling forcoupling the first drive transfer element to the cassette unit and/or tosyringe barrel of the syringe, wherein said first coupling is areversible coupling arranged for decoupling when the syringe moves tothe use position. Thus, in the initial rest position, application ofaxial drive force to the first drive transfer element results inmovement of the syringe as a whole, but in embodiments, not of theplunger relative to the syringe barrel. It may be appreciated that thispreferred initial absence of relative plunger movement is favoured ifthe frictional forces to be overcome in moving the syringe barrel withinthe housing are arranged to be much less than for moving the plungerwithin the syringe barrel. This is typically so since the plunger isoften a natural or synthetic rubber element, which frictionallyinteracts with the sidewall of the syringe barrel. In embodiments, thefirst coupling is a friction clutch coupling arranged for decoupling bydeclutching thereof when the syringe moves to the use position.

In embodiments, once the syringe is in the use position (i.e. needleprotruding) the first coupling decouples (e.g. demounts) such that nocoupling then exists between the first drive transfer element and thesyringe barrel. All further axial drive force applied to the seconddrive transfer element therefore results in plunging axial movement ofthe plunger within the syringe barrel, which acts to drive the liquiddrug formulation contents of the syringe barrel into the hollow needlefor injected delivery from the needle tip.

In embodiments, the first and second drive transfer elements arecomprised as a single drive shuttle element. In embodiments, the shuttlehas an axially symmetric form such as cylindrical form. Guides (e.g. acentral aperture of an end wall) may be provided to the shuttle toassist that axial receipt.

In embodiments, a reset mechanism is provided for resetting the drivearrangement after actuation thereof. In embodiments, the reset mechanismis responsive to the electrically powered source of drive.

It is noted that fundamentally any electrically powered source of driveherein must convert electrical energy (e.g. stored in batteries) intomechanical motion for movement of the syringe and/or cassette unitand/or the plunger. Electric motors typically use electrical energy toproduce rotational motion in the form of a rotating shaft. Variousmethods are well known for conversion of rotational energy into lineardisplacement of the plunger. Conceivable methods are a lead screw andworm gear arrangement, cams, a rack and pinion system or a system ofrigid linkages using the lever principle. The various methods havecertain advantages and disadvantages in terms of complexity, efficiency,mechanical advantage, gearing, maximum displacement velocity, maximumforce etc.

Applicant has appreciated that generally for an injection, it isdesirable to maintain a constant force over the full displacement strokeof the plunger. The performance in terms of maximum velocity and maximumforce of cam and lever based mechanisms will typically vary withposition along the injection stroke such that at extremes of thedisplacement range the maximum force or velocity of the plunger may besubstantially different from that in the centre of the displacementrange. The lead screw and worm gear or rack and pinion systems have theadvantage that they can maintain constant forces over their fulldisplacement range. The velocity of the plunger displacement determinesthe injection time, which is a key parameter in determining patientcomfort. Finally, the maximum force that the electrically powered sourceof drive of the drive unit can produce will determine the limits of drugviscosity and/or needle bore that the device can use in injections. Ingeneral, the maximum plunger velocity and maximum force will beinversely related. That is, higher injection force will limit thevelocity achievable.

In one aspect, an auto-injector drive unit includes a drive unit housingdefining a needle delivery aperture, and the housing is arranged forreceipt of an injection cassette unit. The cassette unit is movable froma rest position, in which a needle tip of the unit is within the driveunit housing, to a use position, in which the needle tip protrudes fromsaid needle delivery aperture. The drive unit also includes a drivearrangement having one or more electrically powered sources of drive, afirst drive transfer element for advancing the cassette unit to the useposition, and a second drive transfer element for ejecting at least partof a liquid drug formulation from the cassette unit. The drive unit isarranged for initial receipt of the cassette unit at an intermediateposition and for transport of the cassette unit to the docking position.

In embodiments, the drive unit is arranged for verification of thecassette unit. The drive unit may include one of an RFID reader and abar code reader, and the drive unit may be arranged for verification ofthe cassette unit at the intermediate position. The drive unit isarranged to transport the cassette unit to the docking position onlyfollowing positive verification of the cassette unit at the intermediateposition.

In embodiments, the drive unit includes a cassette unit holder that ismovable within the drive unit. The cassette unit holder includes acassette unit locking feature for reversibly locking the position of thecassette unit holder within the drive unit.

In one aspect, an auto-injector drive unit includes means for receivingan injection cassette unit, said means defining a needle deliveryaperture. The cassette unit is movable from a rest position, in which aneedle tip of the unit is within the receiving means, to a use position,in which the needle tip protrudes from the receiving means. The driveunit also includes a first drive means for advancing the cassette unitto said us position and a second drive means for ejecting at least partof a liquid drug formulation from the cassette unit. The drive unit isarranged for initial receipt of the cassette unit at an intermediateposition and for transport of the cassette unit to the docking position.

Interaction of Cassette Unit with Drive Unit

The syringe is movable within the drive unit housing from a restposition, in which the needle tip of the syringe is within the driveunit housing to a use position, in which the needle tip protrudes fromthe needle delivery aperture of the drive unit housing.

In embodiments, the syringe is in fixed relationship to the cassetteunit housing and the required movement of the syringe is by movement ofthe cassette unit housing and syringe fixed thereto within the driveunit housing.

In other embodiments, the syringe is in movable relationship to thecassette unit housing and the required movement of the syringe is bymovement of the syringe within the cassette unit housing.

In other embodiments, composite arrangements are envisaged, in which thesyringe movement is achieved by a combination of both movement of thesyringe within the cassette unit housing and by movement of the cassetteunit housing within the drive unit housing.

In embodiments, the drive unit housing and/or any inner drive unithousing sub assembly thereof includes a needle projection aperturethrough which the hollow needle may protrude, for example duringexpelling of the liquid drug formulation through the hollow needle andits needle tip for delivery to the patient.

In embodiments, it is desirable for safety and hygiene reasons that theneedle does not protrude from (i.e. out with) the drive unit housingother than when expelling the liquid drug formulation during aninjection procedure. Thus, the drive unit housing and/or any inner driveunit housing sub assembly thereof and drive unit housing cavity definedthereby is generally arranged such that a needle receiving part thereofallows for the needle of the syringe to be axially moveable therein fromthe rest position in which the needle is wholly housed (or shrouded) bythe needle receiving part to the use position in which at least the tipof the needle protrudes from that needle receiving part of the driveunit housing.

In embodiments, the drive unit housing includes biasing means (e.g. aspring) arranged to act on the syringe and/or the cassette unit housingsuch that the needle of the syringe is normally biased towards the restposition, wherein such biasing means are overcome during the actuationof the syringe (e.g. by an actuating mechanism) to allow for movement ofthe needle to the use position.

In embodiments, it is desirable for drive unit housing to allow for theneedle of the syringe to be retracted into the housing after use. Thus,it is desirable to be able to retract the needle back into the needlereceiving part of the housing after the injection procedure, that is tosay to retract the needle from the use position to a refracted positionthat may in embodiments, correspond to the rest position or in otherembodiments, correspond to a third position, which in embodiments isfurther away from the needle delivery aperture. A needle retractmechanism may thus, be provided (e.g. responsive to a biasing means suchas a light return spring or by reverse action of the drive mechanism) toretract the syringe needle back into the drive unit housing.

In embodiments, it is desirable for the drive unit housing to allow forthe needle of the syringe to be shrouded by a needle shroud elementafter use. Thus, in particular it is desirable to be able to provide ameans of shrouding the needle of the syringe that is moved or otherwisebrought into operation after completion the injection procedure. Suchmeans in embodiments comprises a movable shroud element that is adaptedto be movable to a shrouding configuration at the end of the injectionprocedure.

In embodiments, the drive unit includes a cassette unit holder forholding the cassette unit within the drive unit housing. In embodiments,the cassette unit holder defines one or more inner walls against atleast a part of which the cassette unit seats when held within thecassette unit holder.

In embodiments, the cassette unit holder is sized and shaped such as toallow for a relatively tight clearance between the cassette unit and theinner walls of the cassette unit holder. Such tight tolerances allow forreliable positioning of the cassette unit within the cassette unitholder and drive unit.

In embodiments, the cassette unit holder is mounted within the driveunit for movement along the drive axis, which corresponds to theinjection axis, thereby allowing for movement of the cassette unit andsyringe within the drive unit between its rest and in use (i.e.injected) positions. In embodiments, the cassette unit holder mounts toa linear slide that orients along a direction that is parallel with orcorresponds to the drive axis.

In embodiments, the cassette unit holder is provided with one or morecassette unit locking features for reversibly locking the cassette unitwithin the holder and hence, within the drive unit.

In embodiments, the one or more cassette unit locking features arearranged to be in a locking position when the cassette unit is in thedocking position and in a non-locking position otherwise, including whenthe cassette unit is at the intermediate pre-docking position.

In embodiments, movement of the cassette unit from the intermediatepre-docking position to the docking position results in movement of theone or more locking features from the non-locking to the lockingposition.

In embodiments, each cassette unit locking feature comprises a latchingfeature, lock tab feature or snap-lock feature. In embodiments,engagement of the locking feature provides tactile or audible feedbackto the user as an indication that the cassette unit has been correctlyreceived within the cassette unit holder of the drive unit.

In embodiments, the cassette unit holder is provided with one or morecassette unit locking features protruding from the inner wall(s)thereof. In embodiments, the cassette unit locking features are biasedtowards (e.g. in response to biasing means) or naturally bias towardsthe cassette locking position.

In embodiments, the cassette unit holder has plural (e.g. two) cassetteunit locking features (e.g. snap lock-tabs) integral with and protrudinginwards from the walls thereof.

In embodiments, each of the cassette unit locking features has one ormore angled faces arranged such that the locking feature may be pushedoutwards as a result of force applied to the angled face.

In embodiments, each cassette unit locking feature (e.g. lock tab) hasangled faces at the top and bottom thereof arranged such that thelocking feature (e.g. lock tab) flexes outwards when a force (e.g. froman edge of another mechanical part) is pushed into them from eitherdirection. In embodiments, the angled face at the bottom side of thelocking feature allow for it to flex out of the way as the cassette unitis inserted into the cassette unit holder until the cassette unit isinserted to a holding and locking position, wherein the locking featureflexes back to its original position and lockingly engages the cassetteunit housing. In this position the cassette unit is held in the cassetteunit holder by the locking features (e.g. lock-tabs) because the topfaces of the locking features (e.g. lock-tabs) support the cassetteunit. The angled faces on the top of the locking features (e.g.lock-tabs) also allow for the cassette unit to be pulled out of thecassette unit holder by having the lock-tabs flex outwards in a similarfashion as when a cassette unit is inserted into the cassette unitholder of the drive unit of the auto-injector.

In embodiments, once the cassette unit has been inserted initially intothe cassette unit holder, a reader of the drive unit reads an identifieron the cassette unit to verify details relating to it. Once positiveverification has been established, the cassette unit is transported tothe docking position such as by drawing it into the drive unit. Inembodiments, this receipt of the cassette into the cassette unit holdercorresponds to the pre-docking intermediate position referred tohereinafter.

In embodiments, as the cassette is transported to the docking positionwithin the drive unit, the one or more locking features of the cassetteunit holder are aligned with rigid features within the drive unit thatmaintain the locking features in the locking position such as bypreventing lock-tabs from flexing outwards. Thus, the cassette unit iseffectively locked within the drive unit when the locking features arealigned with these rigid features of the drive unit.

In embodiments, the length of the rigid features of the drive unit arearranged such that the cassette unit cannot be locked in the drive unitwith the needle protruding from the needle delivery aperture such as atany insertion depth of the needle. Typically during the injectionprocess, high loads are transmitted from the plunger through thecassette unit and reacted on the top surfaces of the locking features(e.g. lock-tabs). In embodiments where the top surface is angled, thereis a horizontal component to the reaction load that attempts to flex thelocking features (e.g. lock-tabs) outwards. However, where the lockingfeatures (e.g. lock-tabs) are aligned with (e.g. behind) the rigidfeatures of the drive unit they cannot be flexed outwards and thecassette unit remains rigidly fixed in the drive unit.

In embodiments, once the cassette unit has been received at the dockingposition the removable cap and needle cover attached thereto is removed.Where in embodiments, there is a cap lock feature this must first bereleased. In embodiments, as the cassette is moved to the dockingposition (e.g. by being drawn fully up into the drive unit) the cassetteunit is also brought into contact with cap lock unlocking features,which in embodiments comprise one or more (e.g. two) rigid arms, whichextend into the cassette unit to depress, and thereby to unlock, the caplock feature. In embodiments, the cap lock unlocking features are notrigidly fixed within the drive unit, and the rigid arms thereof thatmove into the cassette unit to depress, and thereby to unlock, the caplock feature pass through cut-outs in the top of the cassette unitholder.

In embodiments, the drive unit is provided with a timer (e.g. timerfunction) that starts a time count on removal of the removable cap andneedle cover from the cassette unit. In embodiments, the timer functionis initiated by the removal of the removable cap and needle cover fromthe cassette unit. In embodiments, the timer counts upwards (i.e. fromzero) on removal of the removable cap and needle cover). In otherembodiments, the timer counts downwards (i.e. from a pre-determined timecount) on removal of the removable cap and needle cover. Thus, forexample an indication of time remaining to safely use the device may becalculated.

In embodiments, the timer is arranged such that on reaching a certain,pre-determined time count a stop command to stop the drive functioningof the drive unit is generated. Drive action of the drive unit is thus,prevented. In embodiments, the stop command is to disable (e.g. switchoff or de-power) said one or more electrically powered sources of axialdrive. In embodiments, the stop command is to initiate a blockingfunction that acts to block the movement of said first and/or seconddrive transfer elements. In embodiments, the timer therefore acts toensure that drug is delivered to the patient within a set time limitfollowing removal of the removable cap and needle cover from the syringeof the cassette unit.

In embodiments, one or more cap removal sensors (e.g. cap removalsensing means) are provided to detect removal of the removable cap andneedle cover from the cassette unit. In embodiments, the one or more capremoval sensors communicate with the timer (e.g. via an electronic dataunit or control unit) to send a cap removal detection signal to thetimer to initiate the time count thereof.

In embodiments, the drive unit includes an electronic display and thetime count is displayed on the electronic display.

In embodiments, to move the cassette unit within the drive unit, a firstdrive transfer element (e.g. a lead-screw) connects to (e.g. bythreading through) a flange connecting to the cassette unit holder.

In embodiments, the cassette unit holder mounts to a linear slide suchthat it is slidably movable in a direction parallel to or correspondingto the drive axis. In embodiments, the first drive transfer element(e.g. lead-screw) couples to the output shaft of a motor/gear-headassembly such as via a universal joint. The universal joint allows formisalignment between the drive axis and the linear slide, which allowsthat the cassette unit holder and motor can be held rigidly in the driveunit without over-constraining the positioning of the cassette unitholder. Over-constraining the cassette unit holder could cause excessivefriction or binding in the threads of the lead-screw and nut and so makehigh accelerations and velocities of the cassette unit holder difficultto achieve.

In embodiments, the lead-screw has four starts and a lead of 6.35 mm.Such a high lead allows for rapid linear accelerations of the cassetteunit holder so that the needle can reach a velocity of 100 mm/sec beforeit pierces the patient's

skin. In embodiments, this mechanism is arranged such as to beback-drivable.

In embodiments, the nut attached to the cassette unit holder has aspecific linear travel for a given rotation of the screw. Inconsequence, the depth the needle is inserted into the patient is set bythe rotational position of the screw. The position of the screw can bedetermined using several means including encoders and monitoringstep-counts, in cases in which the motor being used is a stepper motor.

In embodiments, the drive unit can be configured to provide any suitableneedle insertion depth with a typical needle insertion depth beingbetween about 4 and 8 mm. Once the needle has been inserted into thepatient, the injection of drug may be initiated. To inject the drug,axial drive force is applied to the second drive transfer element (e.g.plunger rod) to drivably move the plunger within the syringe barrel.

In embodiments, to apply the necessary driving load to the syringeplunger a second drive transfer element in the form of lead screw (e.g.a plunger screw) is rotated through a nut that is fixed relative to thesyringe. Since the nut is fixed, the lead screw advances linearly as itis rotated. Having the nut fixed relative to the syringe allows for theplunger screw to stay fixed relative to the syringe when the cassetteunit holder is moved within the device for needle insertion orretraction in an emergency. Otherwise, in embodiments, the plunger screwwould be required to travel the distance that the cassette unit holdermoves during needle insertion prior to its being able to make contactwith the syringe to apply drive load to the syringe plunger. Inembodiments, in the case of emergency retraction when the cassette unitholder needs to be moved into the drive unit in the middle of aninjection, the plunger screw would have to be moved into the drive unitbefore the cassette unit could be rapidly retracted into the drive unit.

In embodiments, during an injection, loads reaching near 60N are appliedto the syringe plunger via the second drive transfer element (e.g. theplunger screw).

In embodiments, the second drive transfer element (e.g. the rotatingplunger screw) could direct undesirably high (e.g. torsion) drive loadson the system if the second drive transfer element makes direct contactwith the syringe plunger. To minimize these torsion loads, the syringebarrel of the cassette unit may be provided with a plunger slaving part.Thus, the second drive transfer element acts to transfer axial drive tothe plunger slaving part and hence, to the plunger of the syringe formoving the plunger into the barrel of the syringe to eject at least partof said volume of liquid drug formulation.

In embodiments, the plunger slaving part is in contact with the plungerof the syringe and is axially movable within the barrel. In embodiments,the plunger slaving part is arranged such that when a drive load isapplied to a rear (e.g. top) drive-receiving face thereof the drive loadis evenly transmitted to the plunger. In embodiments, the plungerslaving part engages (e.g. is in threaded engagement) with the plunger.In embodiments, the diameter of the plunger slaving part corresponds tothe diameter of the plunger.

In embodiments, the plunger is made of a material that is resilientlycompressible (e.g. rubber or an organic polymeric material) and theplunger slaving part is made of a less compressible material. Inembodiments, the plunger slaving part is made of a rigid material (e.g.a hard plastic polymer material such as poly propylene).

In embodiments, the rear face of the plunger slaving part has a centralrecess for receipt of a drive transfer element. In embodiments, thecentral recess is of conical form. Thus in embodiments, the second drivetransfer element defines a drive end arranged for receipt by the centralrecess of the rear drive-receiving face of the plunger slaving part. Inembodiments, the drive end defines a conical tip and said central recessis of conical form to guide and centre said conical tip therein. Inembodiments, the angle of the conical recess is greater than the angleof the conical tip.

In embodiments, the slaving part may be configured to perform a secondpurpose of providing an easy-to-identify visual indicator of theplunger's position within the syringe so that the patient can visuallyconfirm the drug had been fully injected. In this embodiment, theslaving part may be called a stopper position indicator.

In the above described plunger screw embodiment, the plunger screw isrotated through a fixed nut. In consequence, the combination of the highlinear force with the rotating plunger screw could result in hightorsion loads on the system if the plunger screw makes direct contactwith the syringe plunger. To minimize these torsion loads, the plungerscrew is in embodiments, provided with a pointed tip to give rise to apoint load instead of a face load. The pointed tip of the plunger screwmakes contact with a slaving part, which is made of a hard material,thus acting to reduce friction and torsion loads on the system. Theslaving part contacts (e.g. engages) the plunger such that when a loadis applied to its top face the load is evenly transmitted directly intothe plunger. In embodiments, the top of the slaving part has a conicalrecess to guide and centre the pointed end of the plunger screw as it islowered into contact. In embodiments, the angle of the conical recess isgreater than the angle of the conical end of the plunger screw toachieve point contact between the tip of the plunger screw and the topsurface, while also guiding the syringe plunger during its travel.

In embodiments, the plunger screw is rotated by a screw gear, whichreceives drive force from the source of axial drive. In embodiments, theplunger screw slide fits through the center of the gear and is keyed togear via a flat. Since in this embodiment, the plunger screw has a flat,there are sharp corners where the flat is cut across the threads. Inconsequence, reliefs are provided in the walls of pass-through hole inthe screw gear to eliminate the possibility of the thread corners fromcatching on the screw gear as the plunger screw slides through it. Inembodiments, the screw gear is fixed within the device via a press-fitwith a ball bearing that is fixed within the drive unit.

In embodiments, to control the position and angular velocity of thescrew gear, and thus the position and velocity of the plunger screw, thescrew gear is arranged to mesh with a gear mounting to the shaft of amotor/gearhead assembly. In embodiments, the rotation and angularvelocity of the output of the motor/gearhead shaft directly correlatesto the position and velocity of the plunger screw. Thus, the position ofthe plunger screw is determined by the rotational position of the screw.This position of the plunger screw is in embodiments, monitored usingencoders anywhere in the drive train that has rotating components or bymonitoring step-counts if using a stepper motor.

In embodiments, the drive unit is arranged to initially receive thecassette unit housing at an intermediate pre-docking position forsubsequent transport of the cassette unit to the docking position.

In embodiments, the drive unit is arranged to initially receive thecassette unit housing (e.g. at the intermediate pre-docking position orat the docking position) for automated verification thereof. Suchverification can for example, be for the purpose of checking of drug anddosage information, checking that the drug is not past its expiry dateand/or checking that the cassette has not been used previously.

In embodiments, the cassette unit is receivable by a cassette unitholder of the drive unit and the position corresponding to (e.g.initial) receipt of the cassette into the cassette unit holdercorresponds to the intermediate position at which the automaticverification step is carried out.

In embodiments, the cassette unit further comprises an identifier. Theidentifier comprises data in a form that may be readily subject tointerrogation. The drive unit comprises a reader for reading(interrogating) the identifier of the cassette unit and, incommunication with the reader, a verifier for verifying the identifier.

In embodiments, the drive unit is arranged to initially receive thecassette unit housing at the intermediate pre-docking position forautomated verification thereof and the drive unit is arranged such thattransport of the cassette unit to the docking position is permitted onlyfollowing positive verification of the identifier. Thus, onlyappropriately identified cassette units are finally receivable into thedevice to enable injected drug delivery there from.

In embodiments, the identifier may include labelling selected from thegroup consisting of visual text, machine-readable text, bar codes, anddot codes. In embodiments, the identifier is in the form of a passivetransceiver (e.g. an RFID tag) that is interrogable by means of anactive transceiver (e.g. an RFID reader). In embodiments, the identifieris in the form of a bar code that is interrogable by means of a bar codereader.

In embodiments, the cassette unit comprises a first transceiver fortransmitting and receiving data and the drive unit comprises a secondtransceiver for transmitting and receiving data, wherein data istransferable at least from the first transceiver to the secondtransceiver, and in embodiments in two-way fashion from the firsttransceiver to the second transceiver. The data is in embodiments indigital form and suitable for transfer by electronic, radio or opticalmeans.

An advantage of embodiments of this type is the ability to store manytypes of information in different parts of the memory structure of thetransceivers. The information is furthermore stored in a form, which isreadily and accurately transferable. The information could for example,include manufacturing and distribution compliance information written tothe memory at various points in the manufacturing or distributionprocess, thereby providing a detailed and readily accessible producthistory of the cassette unit housing. Such product history informationmay, for example, be referred to in the event of a product recall. Thecompliance information could, for example, include date and time stamps.The information could also include a unique serial number stored inencrypted form or in a password protectable part of the memory, whichuniquely identifies the drug product and therefore may assist in thedetection and prevention of counterfeiting. The information could alsoinclude basic product information such as the nature of the drug anddosing information, customer information such as the name of theintended customer, and distribution information such as the intendedproduct destination.

On loading the drive unit with the cassette unit housing the secondtransceiver may, for example, read the unique serial number, batch codeand expiry date of the drug and any other information on the firsttransceiver. In this way the nature and concentration of the drug in thesyringe of the cassette unit, may be determined. Other information, suchas the date and time of administration of the drug, or environmentalexposure data such as the minimum/maximum temperatures or levels ofhumidity the cassette unit has been exposed to, may also be read anddisplayed to the user. In embodiments, this information is displayed tothe patient on a visual display unit.

Data may also be transferred to and from any transceiver during theperiod of use of the auto-injector by the patient. For example, theauto-injector may include an electronic data system having varioussensors associated therewith. Any data collected by the sensors or fromany data collection system associated with the electronic data systemincluding a clock or other date/time recorder is transferable. Data maybe transferred each time the patient uses the auto-injector. Oralternatively, data may be stored in a database memory of the electronicdata system and periodically downloaded to any transceiver. In eithercase, a history of the usage of the auto-injector may be built up in thememory of any transceiver.

In embodiments, the first and second transceiver each comprise anantenna or equivalent for transmitting or receiving data and connectingthereto a memory. The memory will typically comprise an integratedcircuit chip. Either transceiver may be configured to have a memorystructure, which allows for large amounts of information to be storedthereon. The memory structure can be arranged such that parts of thememory are read-only, being programmed during/after manufacture, otherparts are read/write and further parts are password protectable. Initialtransfer of information (e.g. at the time of manufacture or ofdispensing) to or from any transceiver can be arranged to be readilyachievable by the use of a reader which is remote from theauto-injector, thereby minimising the need for direct product handling.

In embodiments, data is transferable (e.g. in two-way fashion) betweenthe first transceiver on the cassette unit and second transceiver on thedrive unit without the need for direct physical contact therebetween. Inembodiments, data is transferable wirelessly between the first andsecond transceiver.

In embodiments, the second transceiver on the drive unit is an activetransceiver and the first transceiver on the cassette unit is a passivetransceiver. The term active is used to mean directly powered and theterm passive is used to mean indirectly powered.

In embodiments, the first transceiver on the cassette unit comprises anidentifier or tag comprising an antenna for transmitting or receivinginterrogating energy; and an integrated circuit chip connecting withsaid antenna, and the second transceiver on the drive unit comprises areader for said identifier or tag. In this case the identifier or tag isa passive transceiver and the reader is an active transceiver. Inembodiments, the reader is not in direct contact with the tag oridentifier that is to be read.

In embodiments, the integrated circuit chip has a read only memory area,a write only memory area, a read/write memory area or combinationsthereof. In embodiments, the integrated circuit chip has a one-timeprogrammable memory area. In embodiments, the one-time programmablememory area contains a unique serial number. In embodiments, theintegrated circuit chip has a preset memory area containing a factorypreset, non-changeable, unique data item. In embodiments, the presetmemory item is in encrypted form. In embodiments, the integrated circuitchip has plural memory areas thereon. In embodiments, any memory area ispassword protected. In embodiments, any memory area contains data inencrypted form. Electronic methods of checking identity, error detectionand data transfer may also be employed. In embodiments, the integratedcircuit has plural memory areas thereon including a read only memoryarea containing a unique serial number, which may for example beembedded at the time of manufacture; a read/write memory area which canbe made read only once information has been written thereto; and apassword protected memory area containing data in encrypted form whichdata may be of anti-counterfeiting utility.

In embodiments, the tag is on a carrier and the carrier is mountable onthe cassette unit. In embodiments, the carrier comprises an insulatingmaterial such as a glass material or, a paper material or an organicpolymeric material such as polypropylene.

The interrogating energy may be in any suitable form includingultrasonic, infrared, radiofrequency, magnetic, optical and laser form.Any suitable channels may be used to channel the energy including fibreoptic channels.

In embodiments, the first transceiver on the cassette comprises aradiofrequency identifier (RFID) comprising an antenna for transmittingor receiving radiofrequency energy; and an integrated circuit chipconnecting with said antenna, and the second transceiver comprises areader for said radiofrequency identifier. In this case theradiofrequency identifier is a passive transceiver and the reader is anactive transceiver. An advantage of radiofrequency identifier technologyis that the reader need not be in direct contact with the radiofrequencyidentifier tag or identifier to be read.

The radiofrequency identifier can be any known radiofrequencyidentifier. Such identifiers are sometimes known as radiofrequencytransponders or radiofrequency identification (RFID) tags oridentifiers. Suitable radiofrequency identifiers include those sold byPhillips Semiconductors of the Netherlands under the trade marks Hitagand Icode, those sold by Amtech Systems Corporation of the United Statesof America under the trade mark Intellitag, and those sold by TexasInstruments of the United States of America under the trade mark Tagit.

In embodiments, the antenna of the RFID tag is capable of transmittingor receiving radiofrequency energy having a frequency of from 100 kHz to2.5 GHz. Preferred operating frequencies are selected from 125 kHz,13.56 MHz and 2.4 GHz.

In embodiments, the first transceiver on the cassette unit comprises amagnetic identifier or tag comprising an antenna for transmitting orreceiving magnetic field energy; and an integrated circuit chipconnecting with said antenna, and the second transceiver on the driveunit comprises a reader for said magnetic identifier or tag. In thiscase the magnetic identifier or tag is a passive transceiver and thereader is an active transceiver.

In embodiments, the first transceiver on the cassette unit comprises amicroelectronic memory chip and the second transceiver on the drive unitcomprises a reader for said microelectronic memory chip. Themicroelectronic memory chip may comprise an Electrically ErasableProgrammable Read Only Memory (EEPROM) chip, a SIM card-type memory chipor a flash type memory chip. In this case the microelectronic memorychip is a passive transceiver and the reader is an active transceiver.

Once the reader has read (or interrogated) the identifier of thecassette unit, that identifier data is communicated to a verifier, whichconducts a verification step.

In embodiments, the verifier carries out the verification by comparingone or more pieces of data read from the identifier with acceptable datavalues. In embodiments, the comparison makes reference to a look-uptable of acceptable values, which may include data that is patientspecific. In one embodiment, the acceptable values of look-up table arepre-loaded into an electronic data unit of the drive unit. In anotherembodiment, the acceptable values of look-up table are downloadable toan electronic data unit of the drive unit (e.g. by communicating with anonline data source). In one embodiment, the acceptable values of look-uptable are calculable by an electronic data unit of the drive unit (e.g.based on data input by the user or feed-ins from sensors of the device).In one example, the data relates to type of drug with a comparison beingmade between the type of drug contained within the syringe and thatrequired by the patient. In another example, the data relates to the‘use by’ date of the drug with verification being made by reference toan electronic calendar of the electronic data unit of the drive unitwith positive verification being registered only if the ‘use by’ date ofthe drug has not been exceeded. In another example, the data relates tothe ‘lot number’ of the cassette unit and a check is made againstwhether that ‘lot number’ has been subject to a recall or not.

In embodiments, the drive unit is arranged such that transport of thecassette unit from the intermediate position to the docking position ispermitted only following positive verification of the identifier. Thus,only appropriately verified cassette units are finally receivable intothe device for drug delivery there from.

In embodiments, that transport of the cassette unit to the dockingposition is by automatic control under the action of the electricallypowered source of drive. Thus, in embodiments positive verification ofthe cassette unit gives rise to a ‘transport to docking position’ signalfrom the electronic data unit to the source of drive, which results inthe required transporting action.

In embodiments, the drive unit comprises a compartment for storage ofone or more cassette units.

Electronic Data System

In embodiments, the auto-injector additionally comprises an electronicdata system, typically under the control of one or more microcomputers.In embodiments, the electronic data system has input/output capabilityand comprises a memory for storage of data; one or more microprocessorsfor performing operations on said data; and a transmitter fortransmitting a signal relating to the data or the outcome of anoperation on the data. In embodiments, the electronic data system isarranged to be responsive to or activated by the voice of a user. Thus,for example the electronic data system may be switched on or off inresponse to a voice command.

In embodiments, the electronic data system is integral with the driveunit. Alternatively, the electronic data system forms part of anelectronic data unit such as on a circuit board or plug-in, which isreversibly associable with the drive unit.

In embodiments, the drive unit or separable electronic data unitadditionally comprises a data input system for user input of data to theelectronic data system. In embodiments, the data input system comprisesa man machine interface (MMI) in embodiments selected from a keypad,voice recognition interface, graphical user interface (GUI) orbiometrics interface.

In embodiments, the electronic data system additionally comprises avisual display unit for display of data to the user. The display may forexample, comprise a screen such as an LED or LCD screen. In embodimentsthe visual display unit is associable with the drive unit.

In embodiments, the auto-injector additionally comprises a data link forlinking to a local data store to enable communication of data betweenthe local data store and the electronic data system. The data store mayalso comprise data management, data analysis and data communicationcapability.

The data store may itself form part of a portable device (e.g. ahandheld device) or it may be sized and shaped to be accommodated withinthe patient's home. The data store may also comprise a physical storagearea for storage of replacement cassette units. The data store mayfurther comprise an electrical recharging system for recharging anyelectrical energy store of the drive unit, particularly a batteryrecharging system.

The data link may for example enable linking with a docking station, apersonal computer, a network computer system or a set-top box by anysuitable method including a hard-wired link, an infrared link or anyother suitable wireless communications link.

In embodiments, the auto-injector additionally comprises a communicatorfor wireless communication with a network computer system to enabletransfer of data between the network computer system and the electronicdata system. In embodiments, the communicator enables two-way transferof data between the network computer system and the electronic datasystem. Wi-Fi enabled communicators are envisaged.

In embodiments, the data is communicable between the network computersystem and the electronic data system in encrypted form. All suitablemethods of encryption or partial encryption are envisaged. Passwordprotection may also be employed. In embodiments, the communicatoremploys radiofrequency or optical signals.

In embodiments, the communicator communicates via a gateway to thenetwork computer system. In another aspect, the communicator includes anetwork server (e.g. a web server) such that it may directly communicatewith the network.

In a further aspect, the communicator communicates with the gateway viaa second communications device. In embodiments, the secondcommunications device is a telecommunications device, more inembodiments a cellular phone or pager. In embodiments, the communicatorcommunicates with the second communications device using spread spectrumradiofrequency signals. A suitable spread spectrum protocol is theBluetooth (trade mark) standard, which employs rapid (e.g. 1600 times asecond) hopping between plural frequencies (e.g. 79 differentfrequencies). The protocol may further employ multiple sending of databits (e.g. sending in triplicate) to reduce interference.

In embodiments, the network computer system comprises a public accessnetwork computer system. The Internet is one suitable example of apublic access network computer system, wherein the point of accessthereto can be any suitable entry point including an entry point managedby an Internet service provider. The public access network computersystem may also form part of a telecommunications system, which mayitself be a traditional copper wire system, a cellular system or anoptical network.

In another aspect, the network computer system comprises a privateaccess network computer system. The private access network system mayfor example, comprise an Intranet or Extranet, which may for example, bemaintained by a health service provider or drug manufacturer. Thenetwork may for example include password protection; a firewall; andsuitable encryption means.

In embodiments, the communicator enables communication with auser-specific network address in the network computer system. Theuser-specific network address may be selected from the group consistingof a web-site address; an e-mail address and a file transfer protocoladdress. In embodiments, the user-specific network address is accessibleto a remote information source such that information from said remoteinformation source might be made available thereto.

In embodiments, information from the user-specific network address ismade available to the remote information source. In embodiments, theremote information source is a source of drug prescriptions, for examplea doctor's practice or a hospital; a pharmacy; an emergency assistanceprovider; a manufacturer of drugs; or a research establishment.

In embodiments, the auto-injector additionally comprises a geographicpositioning system such as a global positioning system or a system,which relies on the use of multiple communications signals and atriangulation algorithm.

In embodiments, the auto-injector additionally comprises an orientationsensor for checking on the orientation thereof. In embodiments, theauto-injector is arranged to operate only when in certain definedorientations (e.g. upright or nearly so).

Kit of Parts

In embodiments, there is also provided a kit of parts comprising acassette unit (absent syringe) as described above; and a syringecontaining a liquid drug formulation.

In embodiments, there is further provided a kit of parts comprising acassette unit (which may in embodiments, be in kit of parts form) asdescribed above; and a drive unit as described above.

In embodiments, there is further provided a kit of parts comprising anauto-injector (which may in embodiments, be in kit of parts form) asdescribed above; and packaging therefor.

Suitable packaging typically comprises a storage container for the driveunit and one or more cassette units.

In certain implementations, an injection kit includes a cassette unithousing having an inner surface and a plurality of syringe barrelshaving different physical dimensions. The kit may also include aplurality of sleeve form adapters configured to receive at least one ofthe syringe barrels, where the sleeve form adapter has an outer surfaceconfigured to interfit with the inner surface of the cassette unithousing.

In certain embodiments, each syringe barrel has a unique circumferencesize or a unique contoured surface that mates with the sleeve formadapter.

Method of Assembling a Medicament-Injector

In certain implementations, a method of assembly a medicament-injectorincludes selecting a syringe barrel among a plurality of syringebarrels, each of the plurality of syringe barrels having a differentphysical dimension than is found in the other of the plurality. Themethod may also include selecting a sleeve form adapter configured tomate with the selected syringe barrel, interfitting the syringe barrelwithin the sleeve form adapter, and installing the sleeve form adaptorwithin a cassette unit. In certain embodiments, each syringe barrel hasa unique circumference size or a unique contoured surface that mateswith the sleeve form adaptor.

BRIEF DESCRIPTION OF THE DRAWINGS

The disclosure is further described with reference to the accompanyingdrawings, in which:

FIG. 1 is a perspective view of a first cassette unit of anauto-injector herein arranged for use with a 2.25 ml syringe and shownin the ‘pre-use’ configuration;

FIG. 2a is a sectional view taken along line B-B of the first cassetteunit of FIG. 1 now shown in the ‘post-use’ configuration;

FIG. 2b is a sectional view taken along line B-B of the first cassetteunit of FIG. 1 of a detail of the syringe shoulder part of that firstcassette unit, as shown with the end cap removed and also absent syringeplunger;

FIG. 3 is an exploded view of the first cassette unit of FIG. 1;

FIG. 4 is a perspective view of a second cassette unit of anauto-injector herein arranged for use with a 1 ml syringe and shown inthe ‘pre-use’ configuration;

FIG. 5a is a sectional view taken along line A-A of the second cassetteunit of FIG. 4 also in the ‘pre-use’ configuration;

FIG. 5b is a sectional view taken along line A-A of the second cassetteunit of FIG. 4 of a detail of the syringe shoulder part of that secondcassette unit, as shown with the end cap removed;

FIG. 6 is an exploded view of the second cassette unit of FIG. 4;

FIG. 7 is a perspective view of a third cassette unit of anauto-injector herein arranged for use with a 2.25 ml syringe and shownin the ‘pre-use’ configuration;

FIG. 8 is a sectional view of the third cassette unit of FIG. 7 also inthe ‘pre-use’ configuration;

FIG. 9 is an exploded view of the third cassette unit of FIG. 7;

FIG. 10 is a perspective view of a fourth cassette unit of anauto-injector herein arranged for use with a 1 ml syringe and shown inthe ‘pre-use’ configuration;

FIG. 11 is a sectional view of the fourth cassette unit of FIG. 10 alsoin the ‘pre-use’ configuration;

FIG. 12 is an exploded view of the fourth cassette unit of FIG. 10;

FIG. 13 is a part-exploded view of an alternative syringe with shouldersupport assembly suitable for use with any of the cassette units ofFIGS. 1 to 12;

FIG. 14 is a perspective view of the alternative syringe with shouldersupport assembly of FIG. 13;

FIG. 15 is a sectional view of the alternative syringe with shouldersupport assembly of FIG. 13;

FIG. 16 is an exploded view of a removable cap assembly for use with thefirst and second cassette units of FIGS. 1 to 3; and 4 to 6 respectivelyshowing an exemplary mating relationship between a needle cover, aconnector, and a removable cap;

FIGS. 17a and 17b are perspective and cross sectional view of a firstneedle cover for use with the removable cap assembly of FIG. 16;

FIGS. 18a and 18b are perspective and cross sectional view of a rigidneedle shield for use with the needle cover of FIGS. 17a and 17 b;

FIG. 19 is a cross sectional view of the rigid needle shield of FIGS.18a and 18b arranged about the needle cover of FIGS. 17a and 17b and foruse with the removable cap assembly of FIG. 16;

FIGS. 20a to 20c respectively show cross-sectional, cross-sectionaldetail and plan views of the connector and removable cap of the assemblyof FIG. 16;

FIGS. 21a to 21c respectively show cross-sectional, side cross-sectionaland plan views of the removable cap absent connector of the assembly ofFIG. 16;

FIGS. 22a to 22f are various views of the connector for connecting theneedle cover to the removable cap in the assembly of FIG. 16;

FIG. 23 is a plan view of the removable cap assembly of FIG. 16;

FIG. 24 is a perspective view of the removable cap assembly of FIGS. 16and 23 with the removable cap removed for viewing clarity;

FIG. 25 is an exploded view of a fifth cassette unit of an auto-injectorherein arranged for use with a 1 ml syringe;

FIGS. 26a and 26b are sectional views of the fifth cassette unit of FIG.25 at respective, first (pre-use) and second (after-use and recapping)positions;

FIGS. 26c and 26d are perspective and side sectional view of a sixthcassette unit in first (pre-use) position;

FIGS. 26e and 26f are sectional views of the sixth cassette unit in arecapping position and after-use position;

FIGS. 27a and 27b are sectional views showing details of the fifthcassette unit of FIG. 25 at respective, first (pre-use) and second(after-use and recapping) positions;

FIGS. 28a and 28b show sectional views of the fourth cassette unit ofFIGS. 10 to 12 with the cap lock shown in the respective cap locked andcap unlocked positions;

FIG. 29 is a perspective view of a first drive unit, particularlysuitable for use with any of the third to fifth cassette units herein;

FIG. 30 is a perspective view of the first drive unit of FIG. 29 with acassette unit received at the docking position;

FIG. 31 is a perspective view of the first drive unit of FIG. 29 withthe outer cover removed to show the drive arrangement thereof;

FIG. 32 is an exploded view of the first drive unit of FIG. 29 with theouter cover removed to show the drive arrangement thereof;

FIG. 33 is an exploded view of an alternative drive arrangement for usewith the drive unit of FIG. 29, and particularly suitable for use witheither of the first or second cassette units herein, and shown with thefirst cassette unit in non-exploded view;

FIG. 34 is a perspective view of the alternative drive unit of FIG. 33with a cassette unit received at an intermediate, pre-docking position;

FIG. 35 is a sectional view of the alternative drive unit of FIG. 33showing the unlocked relationship between the alternative drive unit andfirst cassette unit present at the intermediate, pre-docking (cassetteunlocked′) position;

FIG. 36 is a sectional view of the alternative drive unit of FIG. 33with the cassette unit now received at the docking (cassette locked′)position;

FIG. 37a is a sectional view of a detail from FIG. 35 showing theunlocked relationship between the drive unit and first cassette unitpresent at the intermediate, pre-docking position;

FIG. 37b is a sectional view of a detail from FIG. 36 showing the lockedrelationship between the drive unit and first cassette unit present atthe docking position;

FIG. 38 is a system drawing of a suitable electronic control system foruse with the drive unit of FIG. 29;

FIGS. 39a to 39i are sectional views showing sequential use steps of afirst drive unit of FIGS. 31 and 32 with a fourth cassette unit of FIGS.10 to 12; and

FIGS. 40a to 40i are sectional views showing sequential use steps of afirst drive unit of FIGS. 31 and 32 with a fourth cassette unit of FIGS.10 to 12, but with the view rotated 90° compared to those views of FIGS.39a to 39 i.

DETAILED DESCRIPTION

To provide an overall understanding of the systems, devices and methodsdescribed herein, certain illustrative embodiments will now bedescribed. For the purpose of clarity and illustration these systems andmethods will be described with respect to auto-injectors that employelectrically powered drive units and cassette units that receivemedicament syringes. It will be understood by one of ordinary skill inthe art that the systems, devices and methods described herein may beadapted and modified as is appropriate, and that these systems, devicesand methods may be employed in other suitable applications, such as forother types of drive units and cassette units, and that other suchadditions and modifications will not depart from the scope hereof.

Referring now to the drawings, FIGS. 1 to 3 show a first cassette unit 1of an auto-injector herein arranged for use with a 2.25 ml syringe.FIGS. 4 to 6 show a second cassette unit that may be appreciated to be avariant of the first cassette unit, but adapted to receive a smaller 1ml syringe. The syringe size may be selected from a wide range of sizes.

The first cassette unit 1 of FIGS. 1 to 3 is arranged for use with asyringe 10 that contains a liquid drug formulation (not shown). Thecassette unit 1 comprises an elongate form cassette unit housing 20 thatis arranged for receipt of the syringe 10 and is sized and shaped forthis purpose. The cassette unit housing 20 is provided with a viewingwindow 22 that allows for viewing of the contents of the syringe 10 tocheck for dispensing thereof. The cassette unit 1 is provided with aremovable cap 50 that is arranged to engage the needle cover comprisingneedle sheath 17 and rigid needle sheath shell 19 of the syringe 10 andthat is shown at FIGS. 1 and 2 in the capped position. Engagement of theneedle cover 17, 19 by the removable cap 50 is by means of cage-likeneedle cover gripper 56, further details of which are described byreference to FIGS. 16 to 24 herein. The cap 50 is provided at the brimthereof with a crown arrangement of first engagement features 52 thatare sized and shaped to extend up into the cassette unit housing 20 whenthe cap 50 is in the capping position. The cap is shaped to define aring pull 54 for receipt by the finger of a user. The interactions ofthe cap 50 with the needle cover 17, 19 and with cap lock feature 40 aredescribed in more detail hereinafter.

The syringe 10 is of a standard 2.25 ml type and comprises a barrel 12with end flange 16 for holding a liquid drug formulation; a hollowneedle 14 at one end of the barrel 12; and a syringe plunger 18 in theform of a rubber stopper that is arranged for axial movement within thebarrel 12 such as to enable the liquid drug formulation to be expelledthrough the hollow needle 14. As shown at FIG. 2, the syringe plunger 18is at the ‘end of use’ position. The hollow needle 14 defines a needlebore, which is of circular cross-section (e.g. 23G, 25G or 27G diameter)and a needle tip 15. The needle tip 15 is sheathed by needle sheath 17,which is provided with rigid needle sheath shell 19. The needle sheath17 and rigid shell 19 in combination define a ‘needle cover’.

The syringe plunger 18 is provided with a slaving part 84 that isreceived as an insert to the rear end of the plunger 18. The slavingpart 84 is arranged to function such that when a load is applied to itstop face the load is evenly transmitted directly into the plunger 18.The rear face of the plunger slaving part 84 has a central recess 93 ofconical form for receipt of a drive transfer element. The slaving part84 is brightly-coloured and performs a second function of providing aneasy-to-identify visual indicator of the position of the plunger 18within the syringe 10 so that the patient can visually confirm the drughad been fully injected.

The cassette unit housing 20 of the cassette unit 1 is arranged todefine a cassette unit housing cavity that is sized and shaped forgenerally fixed receipt of the syringe 10. The cassette unit housing 20defines at its forward end a needle delivery aperture 24 through whichin use, the hollow needle 14 of the syringe 10 protrudes on removal ofthe cap 50 and needle cover 17, 19 there from. Syringe 10 is providedwith an adapter ring 30 that seats adjacent to the end flange 11 of thesyringe barrel 12. The cassette unit housing 20 is also provided with asecurity label 21, which may in aspects be an RFID tag label for use inverification purposes.

The cassette unit 1 is provided with a cap lock feature 40 with lockring 42 arranged for locking interaction with the first engagementfeatures 52 of the removable cap 50 for selectively preventing removalof the cap 50 from the cassette unit housing 20 and also for preventingrotation of the cap 50 relative to the cassette unit housing 20. Adetailed description of the action of this cap lock feature 40 isprovided hereinafter. Cap lock spring 48 fits around the cap lockfeature 40.

Applicant has found that to reduce the risk of the syringe 10 shatteringunder the loads associated with injecting the drug, it is important fora majority of the load path to travel through the forward shoulder 11 ofthe syringe barrel 12 and lesser load to pass through the flange 16 atthe rear end thereof. As most clearly seen by reference to FIG. 2b , theforward shoulder 11 of the syringe 10 is thus, arranged to seat adjacentto an annular shoulder support rim 29 that is defined at the forward endof the inner wall 23 of the cassette unit housing 20. In addition, thebarrel 12 of the syringe 10 interacts with the inner wall 23 of thecassette unit housing 20, which thereby acts to constrain the positionof the syringe 10 within the cassette unit housing 20.

The cassette unit 1 herein may be arranged to accommodate multiplesyringe sizes by providing different shapes and sizes of adapters to thebarrel 12 of the syringe 10. FIGS. 4 to 6 show a second cassette unit101 that is a variant of the first cassette unit 1, but now adapted toreceive a smaller syringe 110 of 1 ml capacity.

Thus, second cassette unit 101 of FIGS. 4 to 6 is arranged for use witha 1 ml syringe 110 that is arranged to contain a liquid drug formulation(not shown). The cassette unit 101 comprises an elongate form cassetteunit housing 120 with security label 121 and viewing window 122 that isarranged for receipt of the syringe 110 and is sized and shaped for thispurpose. The cassette unit 101 is provided with a removable cap 150defining a crown arrangement of first engagement features 152 and ringpull 154, which cap 150 is shown at FIGS. 4 and 5 in the cappedposition.

The syringe 110 is of a standard ‘long’ 1 ml type and comprises a barrel112 with end flange 116 for holding a liquid drug formulation (notshown); a hollow needle 114 at one end of the barrel 112; and a syringeplunger 118 (not visible in FIG. 5b ) in the form of a rubber stopperthat is arranged for axial movement within the barrel 112 such as toenable the liquid drug formulation to be expelled through the hollowneedle 114. As shown at FIG. 5a , the syringe plunger 118 is at the‘pre-use’ position. The hollow needle 114 defines a needle bore, whichis of circular cross-section (e.g. 23G, 25G or 27G diameter) and aneedle tip 115. The needle tip 115 is sheathed by needle sheath 117,which is provided with rigid needle sheath shell 119 to in combinationdefine a ‘needle cover’. As in the first cassette unit, the needle cover117, 119 is engaged by the removable cap 150 by means of cage-likeneedle cover gripper 156, further details of which are described byreference to FIGS. 16 to 24 herein. As before, the syringe plunger 118is provided with a slaving part 184 that inserts into the leading end ofthe plunger 118. The rear face of the plunger slaving part 184 has acentral recess 193 of conical form for receipt of a drive transferelement. The slaving part 184 is also arranged to function as a stopperposition indicator.

The housing 120 of the cassette unit 101 is arranged to define acassette unit housing cavity sized and shaped for generally fixedreceipt of the syringe 110. The cassette unit housing 120 defines at itsforward end a needle delivery aperture 124 through which in use, thehollow needle 114 of the syringe 110 protrudes on removal of the cap 150there from.

Syringe 110 is provided with a sleeve form adapter 130 arranged forreceipt by the outer wall of the syringe barrel 112. The rear end 132 ofthe sleeve form adapter 130 is both flared and provided with pluralslits 134 in the wall thereof such as to define rearward flexiblefingers 138, which allow the adapter 130 to snap-fit over the flange 116of the syringe barrel 116. Thus, the flange 116 of the syringe 110 iseffectively captured by the flange-receiving part 132 of the sleeve formadapter 130. In overall terms, the sleeve form adapter 130 acts tosleeve a major portion of the syringe barrel 112 and end flange 116thereof. The effect of this sleeved relationship is firstly to increasethe effective diameter of the syringe barrel 112; secondly to providestrengthening reinforcement to the end flange 116 thereof; and thirdlyto increase the effective length of the syringe 112.

The sleeve adapter 130 is also provided with plural slits 137 in thewall at the forward end 136 of the sleeve adapter 130 such as to defineforward flexible fingers 138, which allow the forward end of the adapter130 to flex open. The presence of such flexible fingers 138 is ofutility during assembly of the sleeved syringe as the needle cover 117,119 which typically has a larger diameter than the syringe barrel 112,passes through the centre of it when the syringe 110 is pressed into thesleeve adapter 130. The end flange 116 of the syringe 110 then snapsinto the rear end 132 of the sleeve adapter 130 such that the syringe110 is locked into the adapter 130 once assembled.

On a point of detail, adding such a sleeve adapter 130 to the ‘long’(smaller diameter) 1 ml syringe 110 can make it slightly longer than the2.25 ml syringe 10 of FIGS. 1 to 3. Thus, when the cassette unit 1 isassembled with the 2.25 ml syringe, adapter ring 30 is provided adjacentto the syringe flange 16 to make its effective flange thickness the sameas that of the smaller 1 ml syringe 110 with a sleeve adapter 130.

Applicant has found that to reduce the risk of the syringe 110shattering under the loads associated with injecting the drug, it isimportant for a majority of the load path to travel through the forwardshoulder 111 of the syringe barrel 112 and lesser load to pass throughthe flange 116 at the rear end thereof. As most clearly seen byreference to FIG. 5b , the forward end 136 of sleeve adapter 130 fitsaround the forward shoulder 111 of the syringe 110 and thus, defines anannular shoulder support feature 136. That annular support feature 136in turn, seats adjacent to an annular shoulder support rim 129 that isdefined at the forward end of the inner wall 123 of the cassette unithousing 120. When the cap 150 is in place (i.e. as shown at FIG. 5a ),the shoulder support feature 136 fits in snap-relationship between therigid needle sheath shell 119 and the forward shoulder 111 of thesyringe. This snap fitting is typically enabled after the syringeassembly has been pressed through the sleeve adapter 130 during assemblyof the cassette unit 101.

The sleeve adapter 130 for the syringe 110 interacts with the inner wall123 of the cassette unit housing 120, which thereby acts to constrainthe position of the sleeve adapter 130 and syringe 110 within thecassette unit housing 120. The inner wall of the cassette unit housing120 also prevents the flexible fingers 135, 138 of the sleeve adapter130 from flexing outwards when injection loads are applied to thesyringe 110. With the flexible fingers 138 of the forward end 136 of thesleeve adapter 130 securely snapped under the shoulder 111 of thesyringe 110 and so prevented from flexing outwards, the syringe 110 iseffectively secured within the cassette unit housing 101. Were this notto be the case the force applied to the syringe 110 during injectioncould conceivably push the forward fingers 138 open and enable thesyringe 110 to push through.

FIGS. 13 to 15 show different views of an alternative shoulder supportarrangement, which is again arranged such that a majority of the loadpath travels through the forward shoulder 411 of the barrel 412 of thesyringe 410 and lesser load to pass through the flange 416 at the rearend thereof. In embodiments, the shoulder support arrangement allows foraccommodation of manufacturing tolerances and/or acts to prevent shearstress. Variants of this alternative shoulder support arrangement aresuitable for use with any of the cassette units 1; 101; 201; 301described herein.

The alternative shoulder support arrangement makes use of sleeve adapter430 having flexible fingers 438 with end tabs 437 at the forward end 436thereof and securing ring 439 (e.g. formed of metal). In the supportingposition shown at FIGS. 14 and 15, the sleeve adapter 430 seats over theforward shoulder 411 of the syringe 410 and securing ring 439 is pushedforwards up to the end tabs 437 to draw the flexible fingers 438 intosecuring relationship with the forward syringe shoulder 411. Thismovement of the ring 439 to the securing position is typically madeafter the syringe assembly comprising syringe 410 and needle covercomprising needle sheath 417 and rigid needle sheath shell 419 has beenpressed through the sleeve adapter 430 during the assembly operation.

FIGS. 7 to 9 show a third cassette unit of an auto-injector hereinarranged for use with a 2.25 ml syringe. FIGS. 10 to 12 show a fourthcassette unit that may be appreciated to be a variant of the thirdcassette unit, but adapted to receive a smaller 1 ml syringe.

The third cassette unit 201 of FIGS. 7 to 9 is arranged for use with asyringe 210 that contains a liquid drug formulation (not shown). Thecassette unit 201 comprises an elongate form cassette unit housing 220having an end cap 227 that is arranged for receipt of the syringe 210and is sized and shaped for this purpose. The cassette unit housing 220is provided with a viewing window 222 that allows for viewing of thecontents of the syringe 210 to check for dispensing thereof. Thecassette unit housing 220 is further provided with security label 221,which may in aspects be an RFID tag label for use in verificationpurposes. The cassette unit 201 is provided with a removable cap 250that is arranged to engage the needle cover of the syringe 210 that isshown at FIGS. 7 and 8 in the capped position. Label 251 fits over cap250. The cap 250 is provided at the brim thereof with a peripheralarrangement of through-hole first engagement features 252 and also withinsert 266 whose arms protrude out-with the cap 250. The cap 250 isshaped to define a ring pull 254 for receipt by the finger of a user.

Needle cover gripper 256 in the form of a cage-like (or ‘flower’)structure and defining plural gripping elements 258 arranged about acentral hub 259 is further provided to the removable cap 250. Suchgripping elements 258 are arranged for gripping of the needle cover 217,219 on removal of the removable cap 250 such that removal of the cap 250also results in removal of the needle cover 217, 219 and hence,unsheathing of the needle tip 215.

The syringe 210 is of a standard 2.25 ml type and comprises a barrel 212with end flange 216 for holding a liquid drug formulation; a hollowneedle 214 at one end of the barrel 212; and a syringe plunger 218 inthe form of a rubber stopper that is arranged for axial movement withinthe barrel 212 such as to enable the liquid drug formulation to beexpelled through the hollow needle 214. The hollow needle 214 defines aneedle bore, which is of circular cross-section (e.g. 23G, 25G or 27Gdiameter) and a needle tip 215. The needle tip 215 is sheathed by needlesheath 217, which is optionally provided with rigid needle sheath shell(not shown). The needle sheath 217 and optional rigid shell incombination define a ‘needle cover’.

The cassette unit housing 220 of the cassette unit 201 is arranged todefine a cassette unit housing cavity that is sized and shaped forgenerally fixed receipt of the syringe 210. The cassette unit housing220 defines at its forward end a needle delivery aperture 224 throughwhich in use, the hollow needle 214 of the syringe 210 protrudes onremoval of the cap 250 there from. The cassette unit housing 220 definesat its rearward end an end cap 227 adjacent to which the end flange 216of the syringe 210 seats.

The cassette unit 201 is provided with an inner housing sleeve 230 forsleeved receipt of the syringe 210. The cassette unit 201 may bearranged to accommodate multiple syringe sizes by providing innerhousing sleeves 230 of different inner diameter.

The inner housing sleeve 230 also includes cap lock feature 240 arrangedfor locking interaction with the through-hole first engagement features252 of the removable cap 250 and locking arm second engagement features226 of the cassette unit housing 220 for selectively preventing removalof the cap 250 from the cassette unit housing 220 and also forpreventing rotation of the cap 250 relative to the cassette unit housing220

FIGS. 10 to 12 show a fourth cassette unit 301 that is a variant of thethird cassette unit 201, but now adapted to receive a smaller syringe310 of 1 ml capacity.

Thus, fourth cassette unit 301 of FIGS. 10 to 12 is arranged for usewith a 1 ml syringe 310 that is arranged to contain a liquid drugformulation (not shown). The cassette unit 301 comprises an elongateform cassette unit housing 320 with viewing window 322 that is arrangedfor receipt of the syringe 310 and is sized and shaped for this purpose.The cassette unit 301 is again provided with a removable cap 350defining a peripheral arrangement of through-hole first engagementfeatures 352 and ring pull 354, which cap 350 is shown at FIGS. 10 and12 in the capped position. The cap 350 is also provided with insert 366whose arms protrude out-with the cap 350. Label 351 fits over cap 350.Again, the removable cap 350 is provided with a needle cover gripper 356in the form of a cage-like (or ‘flower’) structure and defining pluralgripping elements 358 arranged about a central hub 359.

The syringe 310 is of a standard 1 ml type and comprises a barrel 312with end flange 316 for holding a liquid drug formulation; a hollowneedle 314 at one end of the barrel 312; and a syringe plunger 318 inthe form of a rubber stopper that is arranged for axial movement withinthe barrel 312 such as to enable the liquid drug formulation to beexpelled through the hollow needle 314. The hollow needle 314 defines aneedle bore, which is of circular cross-section (e.g. 23G, 25G or 27Gdiameter) and a needle tip 315. The needle tip 315 is sheathed by needlesheath 317, which is optionally provided with rigid needle sheath shell(not shown). The needle sheath 317 and optional rigid shell incombination define a ‘needle cover’.

The cassette unit housing 320 of the cassette unit 301 is arranged todefine a cassette unit housing cavity that is sized and shaped forgenerally fixed receipt of the syringe 310. The cassette unit housing320 defines at its forward end a needle delivery aperture 324 throughwhich in use, the hollow needle 314 of the syringe 310 protrudes onremoval of the cap 350 there from. The cassette unit housing 320 definesat its rearward end an end cap 327 adjacent to which the flange end 316of the syringe 310 seats.

The cassette unit 301 is provided with an inner housing sleeve 330 forsleeved receipt of the syringe 310. The housing sleeve 330 of thisfourth cassette unit 301 has a smaller effective inner diameter to thatof the housing sleeve 230 of the third cassette unit 201, but has thesame effective outer diameter. Thus, the inner housing sleeve 330 of thefourth cassette unit 301 can function similarly to the sleeve adapter130 of the second cassette unit 101 herein and allow for accommodationof the smaller 1 ml syringe.

Applicant has found that to reduce the risk of the smaller 1 ml syringe310 shattering under the loads associated with injecting the drug, it isimportant for a majority of the load path to travel through the forwardshoulder 311 of the syringe barrel 312 and lesser load to pass throughthe flange 316 at the rear end thereof. Thus, a shoulder support featureis provided in the form of a ring 336 that fits in snap-relationshipbetween the needle cover 317 and the forward shoulder 311 of the syringe310. The inner sleeve housing 330 for the syringe 310 interacts with theinner wall of the cassette unit housing 320, which thereby acts toconstrain the position thereof the sleeve adapter. The inner housingsleeve 330 is further provided with security label 331, which may inaspects be an RFID tag label for use in verification purposes.

In overall terms, the inner sleeve housing 330 acts to sleeve a majorportion of the syringe barrel 312. The effect of this sleevedrelationship is firstly to increase the effective diameter of thesyringe barrel 312. The shoulder support feature 336 also providesreinforcement to the shoulder 311 of the syringe 310.

The inner housing sleeve 330 also includes cap lock feature 340 arrangedfor locking interaction with the through-hole first engagement features352 of the removable cap 350 and locking arm second engagement features326 of the cassette unit housing 320 for selectively preventing removalof the cap 350 from the cassette unit housing 320 and also forpreventing rotation of the cap 350 relative to the cassette unit housing320. More details of this locking arrangement are provided at FIGS. 28aand 28 b.

In each of the first to fourth cassette units 1; 101; 201; 301 describedhereinbefore, a removable cap 50; 150; 250; 350 is arranged to engage aneedle cover 17, 19; 117, 119; 217; 317 by means of a connector 56; 156;256; 356. In each case, removal of the removable cap 50; 150; 250; 350therefore results in removal of the needle cover 17, 19; 117, 119; 217;317 connected thereto such as to allow for ready unsheathing of theneedle tip 15; 115; 215; 315. More detail of this relationship is nowdescribed by reference to FIGS. 16 to 24, which illustrate an exemplaryarrangement of particular relevance to the first and second cassetteunits of FIGS. 1 to 3 and 4 to 6. It will however, be appreciated thatthe underlying concepts now described may be readily be re-applied moregenerally such as to the third and fourth cassette units of FIGS. 7 to 9and 10 to 12 respectively.

FIG. 16 illustrates an exemplary mating relationship between firstneedle cover comprising needle sheath 17, connector 56 and removable cap50 to form in combination a removable cap assembly. The connector 56receives the needle cover 17 and the removable cap 50 receives theconnector 56 having the needle cover 17 enclosed within. In use, thepatient can easily remove the cap assembly 17, 50, 56 and thereby,expose the needle 14 by simply pulling the removable cap 50 away fromthe cassette unit 1. The needle cover 17 of FIG. 16 may readily beadapted to include a rigid needle shield 19, as described in FIGS. 18ato 19.

FIG. 17a depicts a perspective view of an exemplary embodiment of asheath-like needle cover 17, which is cylindrical in shape and defines ashoulder 17 a at the rear end. The needle sheath 17 may be made out ofrubbery material that allows a portion of the connector 56 to dig intothe outer surface thereof, such as that defined by the shoulder 17 a topermanently engage the needle sheath 17 to the connector 56. FIG. 17bshows a cross sectional view of the same needle sheath 17. As depicted,the needle cover 17 includes a needle receiving portion 17 b that isarranged in use, for piercing receipt of the tip 15 of the needle 14 asfor example, shown at FIGS. 2 and 5. In embodiments, the needlereceiving portion 17 b is made from butadiene rubber. In certainembodiments, the needle sheath 17 is hollow, but other shapedarrangements of the interior of the needle sheath 17 are possible suchas the one illustrated at FIG. 19.

FIGS. 18a and 18b show views of a rigid needle shield 19 for use withthe needle sheath 17 of FIGS. 17a and 17b . Rectangular openings 19 aare provided at the rear end of the needle shield for receipt of theshoulder 17 a of the needle sheath 17. FIG. 19 shows the rigid needleshield 19 arranged about the needle sheath 17 to form a needle coverassembly, which is also suitable for use with the removable cap assemblyof FIG. 16. It will be noted that the inner needle-tip receiving part 17b of the needle sheath 17 of FIG. 19 is slightly differently shaped fromthat of the needle sheath 17 of FIGS. 17a and 17b , but otherwise thefunction of the needle sheath 17 is identical.

FIGS. 20a to 20c show various views of the connector 56 in combinationwith the removable cap 50. As shown, the initially cage-like or flowershaped connector 56, as illustrated in FIG. 22a , is bent so as to beconfined within a cylindrical shaped inner cavity 51 of the removablecap 50 (see also FIGS. 21a and 21b ). As a result, a plurality of firstlegs 58 a-58 d, which were initially disposed at about 80 degrees withrespect to the horizontal are now about 90 degrees with respect to thehorizontal. FIG. 20b shows upper internally facing barbs 57 protrudinginwardly and forwardly to engage the needle cover 17 and/or rigid needleshield 19 with a connection that tightens as the removable cap 50 ispulled forwardly. This connection prevents the needle cover 17 and/orrigid needle shield 19 from being removed from the cap when a patientpulls on the removable cap 50 forwardly. FIG. 20c depicts a top view ofthe connector 56 being inserted in the removable cap 50. As shown, whenthe connector 56 is fitted within the removable cap 50, the plurality offirst legs 58 a-58 d engage the inner surface of the removable cap 50and the upper internally facing barbs 57 protrude inwardly and forwardlyfor engaging the needle cover 17 and/or rigid needle shield 19. FIG. 20calso shows the connector 56 including a second plurality of legs 55 a-55b spaced symmetrically away from one another in the forward end of theconnector 56. In some embodiments, the second plurality of legs 55 a-55b are initially disposed more than 90 degrees (e.g., about 91 degrees toabout 120 degrees) with respect to the horizontal. When the connector 56is fitted within the removable cap 50, the second plurality of legs 55a-55 b make contact with the inner surface of the removable cap 50. Insome embodiments, the second plurality of legs 55 a-55 b dig into theinner surface of the removable cap 50 and remain fixed in place duringuse.

The various components of the removable cap 50 are more particularlydescribed with reference to FIGS. 21a to 21c . As shown in FIG. 21a ,the removable cap 50 defines a hollow inner space 51 shaped to receivethe connector 56 and a gripping ring (ring pull′) 54 shaped to receive apatient's finger or thumb. The cap 50 is provided at the brim thereofwith a crown arrangement of first engagement features 52 that are sizedand shaped to extend up into the cassette unit housing 20; 120 (e.g. seeFIGS. 2 and 5) when the cap 50 is in the capping position. The removablecap defines an inner surface forming an orifice 53 (e.g., wider than theinner cavity 51) into which the patient can re-insert the needle afterinjection. As shown, the orifice 53 is wider than the forward end of thesyringe barrel 12; 112.

The fitted relationship between the removable cap 50 and the syringebarrel 12; 112 is shown at FIGS. 2 and 5. The wider orifice 53 helpsreduce the likelihood that a patient will inadvertently stab his or herself when attempting to replace the needle cap after injection. Theinner cavity 51, which may have a cylindrical shape, extends deep intothe cap 50 from the wider orifice. FIG. 21b shows a cross sectional sideview of the removable cap 50 and FIG. 21c shows a top view of theremovable cap 50. As shown, the removable cap 50 is symmetrical aboutits central axis.

The gripping ring 54 defines a finger aperture to receive a patient'sthumb or other preferred finger for pulling the removable cap away fromthe cassette unit 1; 101 to expose the needle 14; 114. In certainembodiments, the finger aperture is adapted to receive a hook that somepatients use to pull the removable cap 50 away from the cassette unit 1;101. The removable cap 50 with gripping ring 54 makes it easier forpatients to engage and disengage the needle cover 17 and/or rigid needleshield 19 from the syringe barrel 12; 112 as it does not require thepatient to contort their fingers by pressing on the sides of a narrowneedle cover 17/19. As noted before, the present auto-injector isintended for use by patients having compromised manual dexterity who maytherefore experience difficulty pulling a conventional needle cover 17and/or rigid needle shield 19 off the syringe 10 before self-injection.The gripping ring 54 addresses this need by allowing the patient tosimply put the thumb or other preferred finger through the fingeraperture 54 and pull on the removable cap to thereby remove the needlecover 17 and/or rigid needle shield 19.

FIGS. 22a to 22f show various views of the connector 56. As shown inFIG. 22a , the connector 56 includes the first plurality of legs 58 a-58d spaced symmetrically away from one another. The connector 56 is made,in certain embodiments, from a thin sheet of stainless steel, formed bya tool that bends the first legs into angles with respect to thehorizontal. Such configuration and the elastic nature of these legs aidin securing the needle cover 17 and/or rigid needle shield 19 to theremovable cap 50. The needle cover 17 and/or rigid needle shield 19 andthe removable cap 50 are also secured together through upper, internallyfacing barbs 57 a-57 c protruding from the first legs 58 a-58 d. Theupper, internally facing barbs 57 a-57 c include tips 60 a-60 b thatpoint toward the forward end of the connector 56 (i.e. the needle tip 15end). As illustrated in FIGS. 22c and 22d , these barbs are spaced aboutthe perimeter of the connector 56 near its proximal end, with each ofthe first legs (e.g. 58 a) having two internally facing barbs (e.g. 57a-57 b), and each barb containing a pair of barb tips (e.g. 60 a-60 b).In some embodiments, the upper, internally facing barbs 57 a-57 c areconcaved as shown in FIGS. 22a to 22d . These barbs are shaped to engagethe needle cover 17 and/or rigid needle shield 19 when the needle cover17 and/or rigid needle shield 19 is fitted within the connector 56. Morespecifically, the barb tips (e.g. 60 a and 60 b) apply opposing forcewith respect to one another when they engage the needle cover 17 and/orrigid needle shield 19 as the barb tips 60 a, 60 b are disposed at twoends of a concaved surface (e.g. upper, internally facing barbs 57 a-57c). In some embodiments, the upper, internally facing barbs 57 a-57 care disposed at an angle with respect to the body of the first legs 58a-58 d. This is more particularly shown in FIG. 22d . Such configurationmay enhance the engagement between the needle cover 17 and/or rigidneedle shield 19 and the connector 56 as added protrusion (i.e., angleddisposition of the barbs 57 a-57 c with respect to the first legs 58a-58 d) allows the barb tips 60 a-60 b to more securely dig into theneedle cover 17 and/or rigid needle shield 19 when a user pulls theremovable cap 50 forwardly. As depicted in FIG. 22d , the longitudinalaxis 61 of the upper portion 62 of the first legs 58 a-58 d is disposedat angle [alpha] with respect to the central axis 63 of the upper,internally facing barb 57 c. The central axis 63 may be disposed betweenabout 3 degrees to about 30 degrees with respect to the longitudinalaxis 61 of the first legs 58 a-58 d.

As noted above, the connector 56 contains a second plurality of legs 55a-55 b spaced symmetrically away from one another in the forward end ofthe connector 56. As shown in FIG. 22e , each of the second plurality oflegs contains lower, externally facing barb tips 64 a-64 d that pointtoward the rear end of the connector 56. These barbs engage a lower,interior portion of the removable cap 50, thereby barbing the connector56 to the removable cap 50 in a manner similar to the connectionsbetween the upper, internally facing barb tips 58 a-58 d and the needlecover 17 and/or rigid needle shield 19 as described above. As the lowerbarbs 64 a-64 d extend proximally into the removable cap 50, these barbs64 a-64 d prevent, in combination with the upper, internally facing barbtips 58 a-58 d, the removable cap 50 from disengaging from the connector56.

FIGS. 23 and 24 depict an exemplary mating relationship between variouscomponents of the removable cap. More specifically, these figures showthe needle cover 17 and rigid needle shield 19 being mated to theconnector 56 and the connector 56 being mated to the removable cap 50.As shown, the connector 56 fits within the removable cap 50 and engagesthe needle cover 17 and/or rigid needle shield 19, connectingsubstantially permanently to the needle cover 17 and/or rigid needleshield 19 such that after engaged, if the removable cap 50 is pulledforwardly by the patient, the entire removable cap 50 and the needlecover 17 and rigid needle shield 19 covering the needle are removed as aunit, exposing the needle 14. In embodiments the rigid needle shield 19is asymmetrical in shape. In embodiments, at least one pair of legs 58a-58 d makes contact with the needle cover 17 and/or rigid needle shield19 such that when the removable cap 50 is pulled, the entire removablecap 50 and the needle cover 17 and rigid needle shield 19 are removed asa unit. In embodiments, only one but not both pairs of legs 58 a-58 dconnect with the needle cover 17 and/or rigid needle shield 19.

FIG. 23 depicts a top view of the removable cap 50 having the needlecover 17 and rigid needle shield 19 received within the connector 56 andthe assembly being fitted within the removable cap 50. As shown, onlythe outermost portions of the first plurality of legs 58 a-58 d arevisible in the top view as the upper, internally facing barbs 57 haveengaged the outer surface of the rigid needle shield 19 and cannot beseen in the top view.

FIG. 24 depicts a perspective view of the assembly as depicted in FIG.23 with the removable cap 50 removed for viewing clarity. The upper,internally facing barbs 57 a-57 b are adapted to receive the needleshield 19 when the needle cover 17 and rigid needle shield 19 areinserted onto the connector 56 in the direction indicated by the arrow,but the upper, internally facing barb tips 60 a-60 b are shaped toengage the needle shield 19 and prohibit backsliding of the needleshield 19 or removal of the connector 56 from the rigid needle shield 19once engaged. As shown, once engaged, the tips 60 a, 60 b of the upperbarbs 57 a-57 b dig into the outer surface of the needle shield 19.

In respect of all of the hereinbefore described cassette units 1; 101;201; 301 the geometry of the removable cap 50; 150; 250; 350 is selectedto allow for the needle cover 17; 117; 217; 317 to be sufficientlyaligned with the needle 14; 114; 214; 314 of the syringe 10; 110; 210;310 so that on re-capping the needle tip 15; 115; 215; 315 does not tendto catch or snag on the needle sheath 17; 117; 217; 317 inside theneedle cover. Applicant has also found that it may be desirable toinclude further features to reduce the risk of needle catching orsnagging on re-capping. FIGS. 25 to 27 b show aspects of a fifthcassette unit 501 that includes such features. The fifth cassette unit501 may be appreciated to be a variant of the fourth cassette unit 301.

The fifth cassette unit 501 is arranged for use with a 1 ml syringe 510that is arranged to contain a liquid drug formulation (not shown). Thecassette unit 501 comprises an elongate form cassette unit housing 520with viewing window 522 and locking arms 526 that is arranged forreceipt of the syringe 510 and inner housing sleeve 530 is sized andshaped for this purpose. The syringe 510 is of a standard 1 ml typehaving a barrel 512, needle 514, needle tip 515, needle cover 517 andother functional components identical to the 1 ml syringe of the fourthcassette unit, which for succinctness are therefore not furtherdescribed. The cassette unit 501 is provided with a removable cap 550and ring pull 554, which cap 550 is shown at FIGS. 26a to 27b in thecapped position. In embodiments, the inner housing sleeve 530 alsoincludes cap lock feature arranged for selectively preventing removal ofthe cap 550 from the cassette unit 501.

The removable cap 550 is provided with a spacer insert 566, whichdefines a central end hub 567. Inner boss 568 extends rearwards from theend hub 567 and defines a needle cover-receiving inner chamber. Outercrenellated boss 569 also extends rearwards from the end hub 567 andincludes in the crenellated portions thereof flexible fingers 565, whichsplay out from the end hub 567 and thus, extend about the outer surfaceof the lower part of outer boss 569. The spacer insert 566 is oftencomprised of a plastic material and may be referred to as a plastic‘outer flower’ structure. Inner chamber of boss 568 of insert 566 of theremovable cap 550 is provided with a needle cover gripper 556 in theform of a cage-like structure and defining plural gripping elements 558arranged about a central hub 559. The needle cover gripper 556 is oftencomprised of a metal and may be referred to as a metal ‘inner flower’structure.

To assist with re-sheathing of the needle cover 517 and needle shield519 on re-capping of the cassette unit 501 after an injection procedure,the position of insert 566 and connector 556 held there-within isarranged within the removable cap 550 such that end hub 567 of thespacer insert 566 is in spaced relationship to the effective end wall549 of the removable cap 550. Having the end hub 567 in somewhat spacedrelationship to the effective end wall 549 of the removable cap 550allows for a certain ‘give’ in the axial position of the needle cover517/shield 519 such that in the event of any snagging of needle cover517/shield 519 by the needle tip 515 during re-sheathing, the spacerinsert 566, connector 556 and needle cover 517/shield 519 is free tomove into the ‘give’ space, thereby ensuring that the snagging eventdoes not result in any bending, or even snapping, of the needle 514. Theoccurrence of any needle stick hazards during re-capping andre-sheathing is thus, minimized. In addition, the presence of ‘give’space ensures that it is always possible to refit the cap 550, which mayotherwise be prevented by needle snagging.

Thus, in the first position of the cassette unit 501 as shown at FIGS.26a and 27a it may be seen that the forward end of the central hub 567of plastic ‘outer flower’ insert 566 is spaced from the end ledge 549 ofthe inner cavity 551 of the removable cap 550. In a second position ofthe cassette unit 501 as shown at FIGS. 26b and 27b , which correspondsto a post-capping configuration following an injection procedure, it maybe seen that the forward end of the central hub 567 of plastic ‘outerflower’ insert 566 has moved into the ‘give’ space and now seats upagainst the end ledge 549 of the inner cavity 551 of the removable cap550. In more detail, after an injection procedure as the user replacesthe removable cap 550 back onto the cassette unit housing 520 the spacerinsert 566 (and connector 556 and needle cover 517/shield 519there-within) is free to move into the ‘give’ space defined betweenforward end of central hub 567 and end ledge 549. This movement willonly happen if resistance to re-capping is created by interaction of theneedle 514/needle tip 515 with the needle cover. By having taken up the‘give’ space, any undue force on the needle 514 during the re-cappingprocedure has been avoided together with any risk of needle bendingand/or snapping as a resulting of snagging events.

In certain implementations, the needle cover gripper 556 connectsdirectly to the removable cap 550 without a spacer insert 566. FIGS. 26Cand 26D show cross sectional views of a sixth cassette unit 601 that isready to be used. As shown, the needle cover gripper 656 is fittedwithin an inner wall 662 of the removable cap 650. An end hub 667 of theneedle cover gripper 656 is positioned at distance d away from the endwall 649 of the removable cap 650. This allows for a certain ‘give’during re-sheathing if the needle tip 615 is misplaced within the needlecover 617/shield 619. More specifically, when the cap 650 is re-insertedonto the cassette, after injection, the removal cap 650 is allowed totravel along the distance d relative to the needle cover gripper 656.But, the force applied by the removal cap 650 during the re-cappingprocess will not transfer directly to the needle cover gripper 656, theneedle cover 617/shield 619, and the needle tip 615. This allows someflexibility for the patient to re-cap the device without beingobstructed in the event the needle snags or gets caught on the side ofthe housing 620 during re-cap. As an example, FIGS. 26E and 26F show theremoval cap 650 being recapped onto the cassette unit housing 620. Moreparticularly, FIGS. 26E-26F show the needle tip 615 being misplaced intothe needle cover 617. The needle tip 615 is now snagged in the side wallof the needle cover 617. Because the removal cap 650 is allowed to moverelative to the needle cover gripper 656 (distance d as shown in FIG.26E), the patient can continue to apply force along the arrow A tocomplete the re-sheathing process, and the removal cap 650 will move inthe direction of arrow A without being impeded by the snagged needle tip615. As shown, the needle cover gripper 656 and the needle cover617/shield 619 will remain fixed in place. The cap 650 moves andoccupies the space left by the distance d between the end wall 649 andthe needle cover gripper 656. FIG. 26F shows the removal cap 650 thathas traveled distance d to recap without breaking or bending themisplaced needle 614.

In respect of all of the hereinbefore described cassette units 1; 101;201; 301 there is provided with a cap lock feature 40, 42; 140, 142;240; 340 arranged for locking interaction with the engagement features52; 152; 252; 352 of the removable cap 50; 150; 250; 350 for selectivelypreventing removal of the cap 50; 150; 250; 350 from the cassette unit1; 101; 201; 301 and also for preventing rotation of the cap 50; 150;250; 350 relative to the cassette unit housing 20; 120; 220; 320.

Details of the cap lock feature 340 of the fourth cassette unit 301 arenow described by reference to FIGS. 28a to 28b . It will be appreciatedthat the general principles of operation of this cap locking functionare applicable to each of the other cassette units 1; 101; 201; 501described herein,

As described previously, the fourth cassette unit 301 comprises anelongate form cassette unit housing 320 with second engagement featuresin the form of locking arms 326 arranged at the forward end thereof. Thecassette unit 301 is provided with a removable cap 350 and ring pull354. Inner housing sleeve 330 also includes cap lock feature in the formof an end-ring 340 arranged for selectively preventing removal of thecap 350 from the cassette unit 301. Operation of this cap lock feature340 is now described.

In both of FIGS. 28a and 28b , engaging tip 329 of each resilientlocking arm 326 of the cassette unit housing 320 protrudes slightly intoa through-hole first engagement feature 352 of the removable cap 350. Itwill be appreciated that this engaging interaction of the angledengaging tip 329 of locking arm 326 with rectangular through-holefeature 352 effectively prevents movement (including rotation) of thecap 350 relative to the cassette unit housing 320. It will also beappreciated that this engaging interaction can be released by pushingeach locking arm 326 inwards, thereby clearing the engaging tip 329 fromengaging relationship with each relevant through-hole 352. As shown,such inward pushing action on the locking arm 326 can be achieved (inthe cap unlocked position of FIG. 28b ) by pulling the cap 350 forwardsand away from the cassette unit housing, which results in the angled tip329 interacting with the wall edges of the through-hole 352 to push thelocking arm 326 inwards. The cap lock feature 340 of the fourth cassetteunit 301 operates by selectively blocking off the possibility of suchinwards pushing action on the locking arms 326 to therefore preventdisengagement of tip 329 from the through-hole 352.

Thus, in the cap locked position of FIG. 28a , cap-lock ring 340 of theinner housing sleeve 330 seats up against the inner face of locking arm326, thereby preventing any inwards movement thereof and so effectivelyalso thereby, preventing any disengagement of the angled tip 329 of thatlocking arm 326 from its through-hole 352. However, in the cap unlockedposition of FIG. 28b , the inner housing sleeve 330 has been movedforwards (e.g. as a result of its interaction with a mover feature ofthe drive unit, as described later) within the cassette unit housing 320to a position in which cap-lock ring 340 of the inner housing sleeve 330no longer seats up against the inner face of locking arm 326. As aresult, inwards movement of the locking arm 326 is no longer preventedand disengagement of the tip 329 of the locking arm 326 from itsthrough-hole 352 is achievable by suitable inwards pushing action on thetip 329/locking arm 326. Such inward pushing action on the locking arm326 is achievable by pulling the cap 350 away from the cassette unithousing, which results in the angled tip 329 interacting with the walledges of the through-hole 352 to push the locking arm 326 inwards.

FIG. 29 shows a drive unit 70 for use with any of the cassette units 1;101; 201; 301; 501 described herein. The drive unit 70 comprises a driveunit housing 71 for housing a drive arrangement 80, which drive unithousing 71 is sized and shaped at its forward end for receipt of acassette unit 1; 101; 201; 301; 501. FIG. 30 shows the drive unit 70having received a representative cassette unit 1 at the dockingposition, wherein ring pull 54 of the removable cap 50 protrudes fromthe drive unit housing 71. The drive unit housing 71 is provided with auser-interface in the form of a screen 72, which may in embodiments be atouch-sensitive screen 72.

FIGS. 31 and 32 shows the inner workings of the drive unit 70 of FIGS.29 and 30, which has been configured in particular for use with thethird, fourth and fifth cassette units 201; 301; 501 herein.User-interface 72 may be seen to communicate with circuit board 74,which comprises electronic system circuitry that provides electroniccontrol for the drive arrangement 80 and data processing capability.Further details of a representative electronic control system herein arelater described by reference to FIG. 38. The circuit board 74 may alsoinclude inputs from various sensors and other electronic componentsincluding radiofrequency ID tag reader 73, which locates on cassetteunit holder 75 and which is arranged for radiofrequency interrogation ofan RFID tag on the cassette unit 1. In other embodiments, theradiofrequency ID tag reader 73 locates at the drive unit at a positioncloser to where the cassette unit 201; 301; 501 is arranged for receipt.

The cassette unit 201; 301; 501 is received and held within the driveunit housing 71 by cassette unit holder 75, which is received withininner holder frame 77, which in turn seats at forward frame end 76,which defines a cassette-unit receiving aperture/needle deliveryaperture 76 a therein. Cassette unit holder 75 mounts within frame 77and is axially (e.g. slidably) movable therein under the selective driveaction of first motor 82. The first motor 82 (e.g. stepper motor)selectively transfers drive via first gear 82 a to a first drivetransfer element in the form of worm 82 b. That worm 82 b interacts witha rack (not visible, but see also FIGS. 40a to 40i ) locating on theback of cassette unit holder 75 to axially move the cassette unit holder75 and cassette unit 201; 301; 501 and syringe 10 held thereby withinthe frame 77 from a rest position, in which the needle 14 with tip 15 ofthe syringe 10 is within the drive unit housing 71 to a use position, inwhich the needle 14 with tip 15 protrudes from the needle deliveryaperture 76 a of the drive unit housing.

Second motor 85 (e.g. stepper motor) selectively communicates via secondgears 83 a, 83 b to a second drive transfer element in the form of athreaded screw 83 c having cover 79 for subsequently transferring axialdrive to the plunger 18 of the syringe 10 for moving the plunger 18within the barrel 12 of the syringe 10 to eject at least part of thevolume of liquid drug formulation contained therein.

FIG. 33 shows the inner workings of a second, alternative drive unit170, which is configured in particular for use with the first and secondcassette units 1; 101 herein as described herein. This drive unit 170 isnow described in relation to its use with a first cassette unit 1, asdescribed previously in relation to FIGS. 1 to 3. The drive unit 170 isshown with the outer housing and electronic system components removedand may be seen to be sized and shaped at its forward end for receipt ofa representative cassette unit 1 having removable cap 50 and ring pull54.

The cassette unit 1 is received and held within the second drive unit170 by cassette unit holder 175, which is received within holder frame177, which at its forward end defines a needle delivery aperture 176therein. The holder frame 177 also defines a pusher arm 190 with rampedend 192 arranged selectively to push flexible locking arm 194 ofcassette unit holder 175 into locking interaction with locking aperture96 of cassette unit 1 as will be described later by reference to FIGS.34 to 37 b. Cassette unit holder 175 attaches via threaded coupling 178to lead screw 179 and is axially drivable thereon under the selectiveaction of the drive arrangement 180. The drive arrangement 180 compriseselectrically powered source of axial drive in the form of a firststepper motor 182. Cassette holder 175 is guided axially on low frictionbearing 191.

First stepper motor 182 selectively communicates via first coupling 183to transfer drive to a first drive transfer in the form of first leadscrew 179 and threaded coupling 178 for moving the cassette unit holder175 and cassette unit 1 and syringe 10 held thereby from a restposition, in which the needle 14 with tip 15 of the syringe 10 is withinthe housing of the drive unit 170 to a use position, in which the needle14 with tip 15 protrudes from the needle delivery aperture 176 of thedrive unit housing.

Second stepper motor 185 also selectively communicates via second gear186 to a second drive transfer element in the form of second lead screw187 for subsequently transferring axial drive to the plunger 18 of thesyringe 10 for moving the plunger 18 into the barrel 12 of the syringe10 to eject at least part of the volume of liquid drug formulationcontained therein.

In embodiments, the drive unit 70; 170 is arranged for sequentialreceipt of a cassette unit 1; 101; 201; 301; 501 herein. Thus, inembodiments, the drive unit 70; 170 is arranged for initial receipt ofthe cassette 1; 101; 201; 301; 501 at an intermediate pre-dockingposition and for subsequent transport of the cassette unit 1; 101; 201;301; 501 to the docking position.

FIGS. 34 to 37 b show aspects of receipt of housing 20 of representativecassette unit 1 provided with removable cap 50 and cap grip ring 54 intoa second drive unit 170. FIGS. 34 and 35 show the cassette unit 1received by the cassette unit holder 175 of the drive unit 170 at anintermediate pre-docking position. As shown in detail at FIG. 37a , inthis intermediate pre-docking position the ramped end 192 of pusher arm190 of holder frame 177 is spaced from, and therefore does not interactin pushing fashion with, the flexible locking arm 194 of cassette unitholder 175. The cassette unit 1 is therefore not yet locked into thecassette unit holder 175. In the fully docking position of FIG. 36, asshown in detail at FIG. 37b , the ramped end 192 of pusher arm hasinteracted with similarly ramped rear end 197 of flexible locking arm194. In consequence, pusher arm 190 of holder frame 177 now pushesagainst flexible locking arm 194 of cassette unit holder 175 to maintainthe locking end 195 thereof in locking interaction with locking aperture196 of cassette unit 1. The cassette unit 1 is therefore now locked intothe cassette unit holder 175. On removal of the cassette unit 1 from thedevice (e.g. post-injection), the inclined upper face 98 of the walldefining the locking aperture 96 acts such as to jack the flexiblelocking arm 194 in the direction as shown at FIG. 37a by arrow A.

In embodiments, the drive unit 70; 170 herein is arranged to initiallyreceive the cassette unit 1; 101; 201; 301; 501 at the intermediatepre-docking position (e.g. of FIGS. 34 and 35) for automatedverification thereof. Such verification can for example, be for thepurpose of checking of drug and dosage information, checking that thedrug is not past its expiry date and/or checking that the cassette hasnot been used previously. In embodiments, the cassette unit 1; 101; 201;301; 501 further comprises an identifier 21; 121; 221; 321; 521 whichmay be an RFID tag and the drive unit 170 comprises a reader 73; 1050for reading (interrogating) the identifier 21; 121; 221; 321; 521 of thecassette unit 1; 101; 201; 301; 501 and, in communication with thereader 73; 1050, a verifier (e.g. part of electronic system 74; 1001)for verifying the identifier 21; 121; 221; 321; 521.

In embodiments, the drive unit 70; 170 is arranged such that transportof the cassette unit 1; 101; 201; 301; 501 to the docking position ispermitted only following positive verification of the identifier 21;121; 221; 321; 521. Thus, only appropriately identified cassette units1; 101; 201; 301; 501 are finally receivable into the device to enableinjected drug delivery there from.

In embodiments, the drive unit 70; 170 is arranged such that transportof the cassette unit 1; 101; 201; 301; 501 from the intermediateposition (e.g. of FIGS. 34 and 35) to the docking position (e.g. of FIG.36) is permitted only following positive verification of the identifier21; 121; 221; 321; 521. Thus, only appropriately verified cassette unitsare finally receivable into the device for drug delivery there from. Inembodiments, that transport of the cassette unit 1; 101; 201; 301; 501to the docking position is by automatic control under the action of theelectrically powered source of drive 82; 182. Thus, in embodimentspositive verification of the cassette unit 1; 101; 201; 301; 501 givesrise to a ‘transport to docking position’ signal from the electroniccontrol unit 74; 1001 to the source of drive, which results in therequired transporting action.

FIG. 38 shows aspects of a typical electronic control system 1001herein. Main microprocessor control unit (MCU) 1010 communicates withthe following:

-   -   Non volatile memory 1020;    -   Power regulating functions comprising serial bus connector 1030,        which is used for power recharge and data communications; power        connector 1032; battery charge controller 1034; rechargeable        battery 1036; voltage regulator 1038 and power distribution        1039;    -   Motor control microprocessor control unit (MCU) 1040 for use in        controlling the drive motor(s) 82, 85, 182, 185 and        communicating with motor drive circuits 1042; insertion motor        82, 182, 1044 and injection motor 85, 185, 1046;    -   RFID reader 1050 with RFID antenna 1052 for use in reading an        RFID tag on the cassette unit 1; 101; 201; 301; 501;    -   Wide Area Network (WAN) radio module 1060 with WAN antenna 1062        for use in communicating to an external computer network;    -   User-interface functions comprising colour display 1070; audio        amplifier 1072 with speaker 1074; power button 1076; go/pause        button 1078; and slow button 1079;    -   Sensing functions namely, cassette detect switch 1080 for        detecting the presence of the cassette within the drive unit;        Cap detect switch 1082 for detecting the presence of the        removable cap 50; 150; 250; 350; 550 on the cassette unit 1;        101; 201; 301; 501; and capacitive touch sense controller 1084        with electrodes 1085 a, 1085 b (many such electrodes may be        present) for detecting the presence of a user's skin;    -   Timer function 1090 (a sub-function of the MCU 1010)

In embodiments, the timer function 1090 of the MCU 1010 is initiated bythe removal of the removable cap 50; 150; 250; 350; 550 and needle cover17; 117; 217; 317; 517 from the cassette unit 1; 101; 201; 301; 501. Inembodiments, cap detect switch 1080 detects removal of the removable cap50; 150; 250; 350; 550 (e.g. together with needle cover 17; 117; 217;317; 517 and rigid needle shield 19; 119; 219; 319; 519) from thecassette unit 1; 101; 201; 301; 501. The timer 1090 then startscounting. In embodiments, once the timer 1090 reaches a certain,pre-determined count a command to cancel the injection (e.g. bypreventing the action of the drive/motor function of the drive unit 70;180) is generated. Drive action of the drive unit 70; 170 is thus,prevented. In embodiments, the timer 1090 therefore acts to ensure thatdrug is delivered to the patient within a set time limit followingremoval of the removable cap 50; 150; 250; 350; 550 (e.g. together withneedle cover 17; 117; 217; 317; 517 and rigid needle shield 19; 119;219; 319; 519) from the cassette unit 1; 101; 201; 301; 501. Examples,of timers that may be used include time or actuation-based countersinstalled on an integrated circuit chip, such as an ePROM. ExampleePROMs include those manufactured by Dallas Semiconductor.

Further aspects of the first auto-injector device herein may now beappreciated by reference to FIGS. 39a to 39i and FIGS. 40a to 40i and tothe following description of a typical use operation: These show anddescribe sequential use steps of a first drive unit 70 essentially inaccord with that already described by reference to FIGS. 31 and 32 asparticularly used in conjunction with a fourth cassette unit 301essentially in accord with that already described by reference to FIGS.10 to 12. The first drive unit 70 includes an electronic control system(not shown) essentially of the type described by reference to FIG. 38.For clarity, only the parts of FIGS. 39a to 39i and 40a to 40i mostrelevant to the use operation being described are identified bylabelling.

Initially, the auto-injector device is in the ‘powered down’ state asshown at FIGS. 39i and 40i , to which it returns after completion of afull use sequence, as described hereinbelow.

In a first stage of a typical use operation and to prepare for use ofthe device, the user hits the power on button 1076 and thereby turns theelectronic control system 1001 on. A ‘welcome message’ is displayed onthe screen 72; 1070 (see FIGS. 29 and 38), which instructs the user toinsert the cassette unit 301.

After power on, the auto-injector device adopts the configuration asshown at FIGS. 39a and 40a , in which the drive unit 70 is initially inthe ‘cassette receipt’ position. The cassette unit holder 75 is in the‘cassette receipt’ position within frame 77. First drive transferelement in the form of worm drive 82 b for movement of the cassette unitholder 75 sets it in the ‘cassette receipt’ position interacting (asvisible in FIG. 40a only) with rack 75 a provided along one side of thecassette holder. Second drive transfer element in the form of threadedscrew 83 c located within cover 79, the threaded screw 83 c serving as aplunger rod 81 (FIG. 39a ), for plunging movement of the plunger 318 ofthe syringe 310 is in its ‘at rest’ position. The cassette unit 301contains a syringe including a syringe plunger 318 that interfaces withthe plunger rod 81 upon activation for delivering medication.

Forward end of the threaded screw 83 c is provided with narrow tippedend-piece 91 arranged for receipt as an insert to the rear end of theslaving part 84 that is in turn, arranged to seat against the rear endof the syringe plunger 318. The general function of the narrow tippedend-piece 91 of the threaded screw is to give rise to a point loadinstead of a face load. The slaving part 84 is made of a hard material,thus acting to reduce friction and torsion loads on the system. Theslaving part 84 is arranged to function such that when a load is appliedto its top face the load is evenly transmitted directly into the syringeplunger 318. In embodiments, the slaving part 84 is brightly-colouredand performs a second function of providing an easy-to-identify visualindicator of the position of the plunger 318 within the syringe 310 sothat the patient can visually confirm the drug had been fully injected.Sprung-loaded cassette unit-unlock cams 88 a, 88 b, the function ofwhich will be described later, are also in their ‘at rest’ positions.

In a second stage of a typical use operation, as shown at FIGS. 39b and40b , the user inserts cassette unit 301 comprising syringe 310 andhaving removable cap 350 to the intermediate pre-docking position withinthe cassette unit holder 75 of the drive unit 70. In this positionslaving part 84 seats up against syringe plunger 318 at the rear flange316 end of the syringe 310.

As shown at FIG. 39b , in the intermediate pre-docking position thecassette unit 301 is locked into the cassette unit holder 75. Thus,flexible locking arms 94 of the cassette locate within locking apertures96 of cassette unit holder 75. FIG. 39b also shows a port 87 that isdisposed on the cassette unit 301 near the proximal region of thesyringe 310. The port 87 is shaped and sized to receive the plunger rod81 that is installed on the drive unit. In certain implementations, theport 87 defines a passageway into the cassette unit 301 through whichthe plunger rod 81 advances to drive the plunger 318 within the barrel312 of the syringe 310. FIG. 28a shows a cross sectional view of anembodiment of the port 87. As shown, the port 87 includes a distal leg99 that is received within the flange 316 of the syringe 310. The port87 also includes an inner rim 97 for receiving the plunger rod 81 (FIG.39b ) and a top surface 103 that engages a distal portion of the driveunit. When the cassette unit 301 is mated to the drive unit 70, theplunger rod 81 of the drive unit 70 enters the port 87 to engage thesyringe plunger 318 housed within the syringe 310.

As shown at FIG. 40b , in the intermediate pre-docking position, theremovable cap 350 is in the cap locked position (also see FIG. 28a ).Thus, cap-lock ring 340 of the inner housing sleeve 330 seats up againstthe inner face of locking arm 326, thereby preventing any inwardsmovement thereof and so effectively also thereby, preventing anydisengagement of the angled tip 329 of that locking arm 326 from itsthrough-hole 352.

Verification of the cassette unit 301 occurs at this intermediatepre-docking position. Thus, RFID reader 73; 1050 (see FIGS. 32 and 38)of the drive unit interrogates RFID tag 21 (see FIG. 3) of the cassetteunit 301 and thereby, reads verification information from the RFID tag21 of the cassette unit 301. Such verification can for example, be forthe purpose of checking of drug and dosage information, checking thatthe drug is not past its expiry date and/or checking that the cassetteunit 301 has not been used previously.

Upon positive verification of the cassette unit 301, the cassette unitholder 75 and cassette unit 301 are drawn further up (i.e. transported)into the drive unit 70 to the docking position of third stage of atypical use operation of FIGS. 39c and 40c . Such drawing up is achievedby the drive action of worm drive 82 b on rack 75 a of the cassette unitholder. The worm drive 82 b receives axial drive from first motor 82;1042 via gear 82 a in response to a command from motor drive circuits1042 acting under the control of motor control MCU 1040, which in turncommunicates with main MCU 1010.

It will be noted that in the docking position, the threaded screw 83 chas been drawn deeper into its cover 79. It will also be noted thatend-ring 354 of removable cap 350 still protrudes out with the exitaperture 76 a of drive 70, but otherwise the cassette unit 301 is fullywithin the drive unit 70.

As shown at FIG. 40c , in the docking position, the removable cap 350 isin the cap-unlocked state (also see FIG. 28b ). Thus, inner housingsleeve 330 may be seen to have been moved relative to the cassette unit301 to a position in which cap-lock ring 340 of the inner housing sleeve330 no longer seats up against the inner face of locking arm 326. As aresult, inwards movement of the locking arm 326 is no longer preventedand disengagement of the tip 329 of the locking arm 326 from itsthrough-hole 352 is achievable by suitable inwards pushing action on thetip 329/locking arm 326. Such inward pushing action on the locking arm326 is achievable by pulling the cap 350 away from the cassette unit301, which results in the angled tip 329 interacting with the wall edgesof the through-hole 352 to push the locking arm 326 inwards.

The screen 72; 1070 now displays an instruction to the user to removethe cap 350 of the cassette unit 301. The drive unit 70 is provided witha timer function 1090, which is initiated by the removal of theremovable cap 350 from the cassette unit 301. Cap removal sensing means1082 are provided to detect removal of the removable cap 350 from thecassette unit 301. The timer 1090 then starts counting. In embodiments,once the timer 1090 reaches a certain, pre-determined count a command toprevent the drive function 80 of the drive unit 70 is generated. Driveaction of the drive unit 70 is thus, prevented. The timer therefore actsas a safety measure to ensure that drug is delivered to the patientwithin a set time limit following removal of the removable cap 350 fromthe cassette unit 301.

In a fourth stage of a typical use operation, as shown at FIGS. 39d and40d , the user has removed the cap 350 together with needle cover 317and rigid needle shield 319. The needle 314 with tip 315 of the syringe310 is now uncovered, but still shrouded by the drive unit 70 and doesnot protrude from the exit aperture 76 a thereof. The screen 72; 1070now displays an instruction to the user to place the device (i.e. theexit aperture 76 a thereof) against the injection site. Once the exitaperture 76 a has been placed against the injection site electrodes 1085a, 1085 b of capacitive touch sense controller (e.g. skin sensor)register the correct placing of the device at the injection site. Thescreen 72; 1070 now displays an instruction to the user to initiate theinjection by pressing the ‘inject’ button. In other embodiments, suchinitiation of the injection may be configured to occur automatically onsensing of the correct placing of the device at the injection site.

In a fifth stage of a typical use operation, as shown at FIGS. 39e and40e , the syringe 310 has now been advanced to the injection position,in which the tip 315 of the needle 315 protrudes outwith the exitaperture 76 a. Such advancement of the syringe 310 has been achieved byforward movement of the cassette unit holder 75, which is responsive tothe forward driving action of worm drive 82 b on rack 75 a of thecassette unit holder 75. The worm drive 82 b receives axial drive fromfirst motor 82; 1042 via gear 82 a in response to a command from motordrive circuits 1042 acting under the control of motor control MCU 1040,which in turn communicates with main MCU 1010. It will also be notedthat in the injection position, the threaded screw 83 c has been drawnforwards and slightly from its cover 79.

Once the syringe 310 is at the injection position of FIGS. 39e and 40e ,ejection of drug from the syringe barrel 312 can commence. Such ejectionin response to forward advancement of threaded screw 83 c responsive togeared driving by gears 83 a, 83 b, which receive axial drive fromsecond motor 85; 1046 in response to a command from motor drive circuits1042 acting under the control of motor control MCU 1040, which in turncommunicates with main MCU 1010. Threaded screw 83 c via end-piece 91acts on slaving part 84 such that forward advancement thereof results inforward moving of that slaving part 84, which in turn results inplunging movement of the plunger 318 within the barrel 312 of thesyringe 310 to expel the drug formulation contents through the tip 315of the needle 314 and into the injection site (e.g. skin of the user).The slaving part 84 functions such that when a driving load is appliedto its top face by end-piece 91 of threaded screw 83 c the load isevenly transmitted directly into the syringe plunger 318.

To reduce the risk of the syringe 310 shattering under the loadsassociated with injecting the drug, it is important for a majority ofthe load path to travel through the forward shoulder 311 of the syringebarrel 312 and lesser load to pass through the flange 316 at the rearend thereof. It may therefore be seen that forward shoulder 311 of thesyringe 310 is surrounded by an annular shoulder support ring 330, whichseats against the forward end of the inner wall 323 of the cassette unithousing 320. Information related to the progress of the injection may bedisplayed on the screen 72; 1070 including for example, a signal that‘injection has been completed successfully’.

In a sixth stage of a typical use operation, as shown at FIGS. 39f and40f , post-completion of the injection, the needle 314 with tip 315 ofthe syringe 310 has been withdrawn back into the drive unit 70 into theremovable cap unlocking position. Such withdrawal of the syringe 310 isachieved by rearwards movement of the cassette unit holder 75, which isresponsive to the rearward driving action of worm drive 82 b on rack 75a of the cassette unit holder 75. The worm drive 82 b receives axialdrive from first motor 82; 1042 via gear 82 a in response to a commandfrom motor drive circuits 1042 acting under the control of motor controlMCU 1040, which in turn communicates with main MCU 1010.

It will be noted in the post-injection position of FIGS. 39f and 40fthat threaded screw 83 c with end-piece 91 has been advanced forwardsufficiently to drive both slaving part 84 and the plunger 318 withinthe barrel 312 of the syringe 310 fully forwards. Thus, the leading endof the plunger 18 locates adjacent to the neck 311 of the syringe 310.The slaving part 84 is brightly-coloured and performs a secondaryfunction of providing an easy-to-identify visual indicator of theposition of the plunger 318 within the syringe 310 so that the patientcan visually confirm the drug had been fully injected. The screen 72;1070 now displays a message instructing the user to replace the cap 350.

In a seventh stage of a typical use operation, as shown at FIGS. 39g and40g , the cap 350 with needle cover 317 and rigid needle shield 319 hasnow been replaced on the cassette unit 301 following completion of theinjection procedure. At this stage, the cassette unit 301 is still inlocked engagement with the cassette unit holder 75 and removal of thecassette unit 301 is therefore not possible. Threaded screw 83 c withend-piece 91 has been withdrawn to the ‘at rest’ position.

In an eighth stage of a typical use operation, as shown at FIGS. 39h and40h , the cassette unit holder 75 and cassette unit 301 carried therebyhave been moved to a cassette unlock position forward of the ‘cassettereceipt’ position of FIGS. 39b and 40b . Such return is achieved by thedrive action of worm drive 82 b on rack 75 a of the cassette unitholder. The worm drive 82 b receives axial drive from first motor 82;1042 via gear 82 a in response to a return command from motor drivecircuits 1042 acting under the control of motor control MCU 1040, whichin turn communicates with main MCU 1010.

As the cassette unit holder 75 is returned forwards the leading edgethereof interacts with sprung-loaded cassette unit-unlock cams 88 (onlyone labeled) to move them from their ‘at rest’ to ‘actuated’ positions.When in the ‘actuated’ position the rounded head 89 of cam 88 presses onengaging tip 95 of locking arm 94 to move that locking arm 94 out oflocking engagement with the locking aperture and thus, to allow thecassette unit 301 to be released from the cassette unit holder 75.

The screen 72; 1070 now displays a message instructing the user toremove the cassette unit 301 from the drive unit 70. The useraccordingly removes the cassette unit 301 to leave the drive 70 in thecassette unlock position as shown at FIGS. 39i and 40i , which remainswhen the device is turned off.

The screen 72; 1070 then displays a message confirming that the cassetteremoval operation is complete. A battery check and/or data communicationstep may also be performed. The user then hits the power button to turnthe drive unit off and the drive unit is stowed in cassette unlockposition until powered-up for a subsequent injection operation.

The auto-injector of the invention is suitable for the injected deliveryof drug, particularly for the treatment and/or prophylaxis of a numberof diseases, disorders or conditions, including infections (viral, e.g.HIV infection, bacterial, fungal and parasitic); endotoxic shockassociated with infection; inflammatory diseases/autoimmunity such asosteoarthritis, rheumatoid arthritis, psoriatic arthritis, systemiclupus erythematosus (SLE), ankylosing spondilitis, COPD, asthma,Alzheimer's Disease, Crohn's disease, ulcerative colitis, irritablebowel syndrome and psoriasis; immune mediated inflammatory disorders ofthe central and peripheral nervous system such as multiple sclerosis andGuillain-Barr syndrome; graft-versus-host disease; organ transplantrejection; pain; cancer (including solid tumours such as melanomas,hepatoblastomas, sarcomas, squamous cell carcinomas, transitional cellcancers, ovarian cancers and hematologic malignancies, acute myelogenousleukaemia, chronic myelogenous leukemia, gastric cancer and coloncancer); congenital disorders, e.g. cystic fibrosis and sickle cellanaemia; growth disorders; epilepsy; treatment of infertility; heartdisease including ischaemic diseases such as myocardial infarction aswell as atherosclerosis and intravascular coagulation; bone disorderssuch as osteopenia and osteoporosis; and metabolic/idiopathic disease,e.g. diabetes.

In embodiments, the syringe of the auto-injector herein contains aliquid drug formulation, which is designed for refrigerated rest (e.g.at from 2-8° C.) and for injected delivery at room temperature (e.g. ator about 18-30° C.). In embodiments, the viscosity of the liquid drugformulation is less than 120 mPa·s (120 centipoise), in embodiments lessthan 100 mPa·s (100 centipoise) at a delivery temperature of 20° C.

Appropriate drugs may thus be selected from biologically active agents,including chemical entities, polysaccharides, steroids and, especially,naturally occurring and recombinant proteins, including glycoproteins,polypeptides and oligopeptides and polymeric derivatives thereof.Particular proteins, polypeptides and oligopeptides include hormones,such as insulin, epinephrine, norepinephrine, adrenocorticotrophin,somatotropin, erythropoietin and oxytocin; cytokines, such aslymphokines, chemokines and interleukins and receptors therefor, e.g.interleukin (IL)-1α, IL-1β, IL-1R, IL-2, IL-3, IL-4, IL-5, IL-6, IL-13,IL17, interferon (IFN)-α, IFN-β, IFN-γ, granulocyte monocyte colonystimulating factor, tumour necrosis factor-α; growth factors, such asnerve growth factor and platelet-derived growth factor; enzymes, such astissue plasminogen activator; and, especially, immunoglobulins.Immunoglobulins include whole antibodies and functionally activefragments and/or derivatives thereof, for example polyclonal,monoclonal, recombinant, multi-valent, mono- or multi-specific,humanised or chimeric antibodies, single chain antibodies, Fabfragments, Fab′ and F(ab′)₂ fragments. Polymeric derivatives of suchproteins, polypeptides and oligopeptides include derivatives formedbetween the protein, polypeptide or oligopeptide and a naturallyoccurring or synthetic polymer, e.g. a polysaccharide or a polyalylklenepolymer such as a poly(ethyleneglycol) [PEG] or derivative thereof, e.g.methoxypoly(ethyleneglycol) [mPEG]. Particular agents include growthhormones and hormones for the treatment of infertility. Other particularagents are for the treatment of epilepsy such as brivaracetam andseletracetam.

The auto-injector device herein has been found to be of particularutility where the drug is an immunoglobulin or a fragment thereof,especially a PEGylated or mPEGylated antibody fragment.

The liquid drug formulations herein are typically aqueous formulations,which comprise the drug in solution and additionally other optionalformulation components, which may include buffers (e.g. lactate,acetate), NaCl, and pH modifiers (e.g. NaOH).

The auto-injector device herein has been found to be of particularutility wherein the concentration of the drug (e.g. a therapeuticbiologic type drug) in the liquid drug formulation is quite high. Inparticular, where the drug is a pegylated antibody the auto-injectordevice has been found to be of particular utility wherein theconcentration of the drug is greater than 100 mg/ml, particularlygreater than 150 mg/ml such as 200 mg/ml.

It is to be understood that the foregoing description is merelyillustrative and is not to be limited to the details given herein. Whileseveral embodiments have been provided in the present disclosure, itshould be understood that the disclosed systems, devices, and methods,and their components, may be embodied in many other specific formswithout departing from the scope of the disclosure.

Variations and modifications will occur to those of skill in the artafter reviewing this disclosure. The disclosed features may beimplemented, in any combination and subcombinations (including multipledependent combinations and subcombinations), with one or more otherfeatures described herein. The various features described or illustratedabove, including any components thereof, may be combined or integratedin other systems. Moreover, certain features may be omitted or notimplemented. Examples of changes, substitutions, and alterations areascertainable by one skilled in the art and could be made withoutdeparting from the scope of the information disclosed herein. Allreferences cited herein are incorporated by reference in their entiretyand made part of this application.

The application of which this description and claims form part may beused as a basis for priority in respect of any subsequent application.The claims of such subsequent application may be directed to any featureor combination of features described herein. They may take the form ofproduct, method or use claims and may include, by way of example andwithout limitation, one or more of the following claims.

The invention claimed is:
 1. An auto-injector comprising: a cassetteunit comprising an identifier and a cassette unit housing defining acassette unit housing cavity, said cassette unit housing cavity arrangedfor receipt of a syringe comprising: a barrel for containing a volume ofa liquid drug formulation; a hollow needle at a front end of saidbarrel, said hollow needle defining a needle tip for dispensing of saidliquid drug formulation; and a plunger that is axially movable withinthe barrel; and a drive unit comprising: a drive unit housing defining adocking cavity and a needle delivery aperture, wherein said dockingcavity is arranged for docking receipt of the cassette unit at a dockingposition, whereupon said cassette unit and/or said syringe is movablefrom a rest position, in which the needle tip of the syringe is withinthe drive unit housing to a use position, in which the needle tipprotrudes from said needle delivery aperture; a reader for reading saididentifier; a verifier, in communication with said reader, for verifyingsaid identifier; a drive arrangement, said drive arrangement comprising:one or more electrically powered sources of axial drive; a first drivetransfer element for transferring said axial drive to the cassette unitand/or to the syringe for advancing the syringe to said use position;and a second drive transfer element for subsequently transferring theaxial drive to said plunger of the syringe for moving the plunger intothe barrel of the syringe to eject at least part of said volume ofliquid drug formulation; and a cassette unit holder for holding thecassette unit within the drive unit housing, said cassette unit holderhaving a flexible locking arm arranged for locking interaction with alocking aperture of the cassette unit, wherein said drive unit isarranged for initial receipt of the cassette unit at an intermediatepre-docking position and for subsequent transport of the cassette unitto the docking position, wherein said drive unit is arranged forverification of the cassette unit at the intermediate pre-dockingposition, wherein the drive unit is arranged such that transport of thecassette unit to the docking position is permitted only followingpositive verification of the identifier at the intermediate pre-dockingposition, wherein at the intermediate pre-docking position, the flexiblelocking arm does not interact with the locking aperture and at thedocking position the flexible locking arm interacts in locking fashionwith the locking aperture to lock the cassette unit within the cassetteunit holder, wherein the drive unit further comprises a holder framedefining a pusher arm, wherein in the intermediate pre-docking positionsaid pusher arm of said holder frame is spaced from, and therefore doesnot interact with, the flexible locking arm of the cassette unit holder,and wherein in the docking position the pusher arm interacts with theflexible locking arm to push the flexible locking arm of the cassetteunit holder into locking interaction with the locking aperture of thecassette unit.
 2. An auto-injector according to claim 1, wherein saididentifier comprises an RFID tag and said reader is an RFID reader orwherein said identifier comprises a bar code and said reader is a barcode reader.
 3. An auto-injector according to claim 1, wherein transportof the cassette unit to the docking position is by automatic controlunder the action of the electrically powered source of drive.
 4. Anauto-injector according to claim 1, wherein the cassette unit holder ismovable within the drive unit, thereby allowing for movement of thecassette unit within the drive unit.
 5. An auto-injector according toclaim 4, wherein the cassette unit holder mounts to a linear slide thatorients along a direction that is parallel with or corresponds to thedrive axis.
 6. An auto-injector according to claim 1, wherein thecassette unit holder is provided with one or more cassette unit lockingfeatures for reversibly locking the cassette unit there within.
 7. Anauto-injector according to claim 6, wherein the one or more cassetteunit locking features are arranged to be in a locking position when thecassette unit is in the docking position and in a non-locking positionotherwise.
 8. An auto-injector according to claim 6, wherein transportof the cassette unit from the intermediate pre-docking position to thedocking position results in movement of the one or more locking featuresfrom the non-locking to the locking position.
 9. An auto-injectoraccording to claim 8, wherein at the docking position the one or morelocking features of the cassette unit holder align with rigid featureswithin the drive unit that maintain the locking features in the lockingposition.
 10. An auto-injector according to claim 6, wherein each or anyof the cassette unit locking features comprises a latching feature, locktab feature or snap-lock feature.
 11. An auto-injector according toclaim 6, wherein each or any of the cassette unit locking features biastowards the cassette locking position.
 12. An auto-injector according toclaim 1, wherein the housing receives a syringe containing a liquid drugformulation.
 13. An auto-injector according to claim 12, wherein theliquid drug formulation comprises an aqueous formulation of atherapeutic biologic type drug.
 14. An auto-injector according to claim1, wherein the pusher arm of the holder frame has a ramped end and theflexible locking arm of the cassette unit holder has a ramped end. 15.An auto-injector drive unit comprising: a drive unit housing defining aneedle delivery aperture, wherein the housing is arranged for receipt ofan injection cassette unit, whereupon said cassette unit comprises anidentifier and is movable from a rest position, in which a needle tip ofthe unit is within the drive unit housing, to a use position, in whichthe needle tip protrudes from said needle delivery aperture; a readerfor reading said identifier; a verifier, in communication with saidreader, for verifying said identifier; a drive arrangement, said drivearrangement comprising: one or more electrically powered sources ofdrive; a first drive transfer element for advancing the cassette unit tosaid use position; and a second drive transfer element for ejecting atleast part of a liquid drug formulation from the cassette unit; and acassette unit holder for holding the cassette unit within the drive unithousing, said cassette unit holder having a flexible locking armarranged for locking interaction with a locking aperture of the cassetteunit, wherein said drive unit is arranged for initial receipt of thecassette unit at an intermediate position and for transport of thecassette unit to the docking position, wherein said drive unit isarranged for verification of the cassette unit at the intermediatepre-docking position, wherein the drive unit is arranged such thattransport of the cassette unit to the docking position is permitted onlyfollowing positive verification of the identifier at the intermediatepre-docking position, wherein at the intermediate pre-docking position,the flexible locking arm does not interact with the locking aperture andat the docking position the flexible locking arm interacts with thelocking aperture to lock the cassette unit within the cassette unitholder, and wherein the drive unit further comprises a holder framedefining a pusher arm, wherein in the intermediate pre-docking positionsaid pusher arm of said holder frame is spaced from, and therefore doesnot interact with, the flexible locking arm of the cassette unit holder,and wherein in the docking position the pusher arm interacts with theflexible locking arm to push the flexible locking arm of the cassetteunit holder into locking interaction with the locking aperture of thecassette unit.
 16. An auto-injector drive unit according to claim 15,wherein said drive unit comprises one of an RFID reader and a bar codereader.
 17. An auto-injector drive unit according to claim 15, whereinthe pusher arm of the holder frame has a ramped end and the flexiblelocking arm of the cassette unit holder has a ramped end.